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This work was funded by grants from MINECO (BFU2014-59796-R to A. A. and BIO2014-52537-R to P.L.R.). J.L.-J was supported by a Juan de la Cierva contract from MINECO and by the Marie Sklodowska-Curie Action H2020-MSCA-IF-2015-707477.

Reactions of N,N-diisopropylisonicotinamide (L) with anhydrous CuCl2, CuBr2 and Cu(ClO4)2·6H2O yielded: (a) an ionic product with the molecular composition of [CuL2(H2O)4]·2[CuLCl3] 1; (b) a coordination polymer [CuL2Br2]n 2 and (c) a mononuclear complex [CuL4(C3H8O)2]·(ClO4)2] 3, respectively. Similarly, the reaction of N,N-diisobutylisonicotinamide (L′) with Cu(NO3)2·3H2O yielded a coordination polymer [{CuL′2(H2O)2}(NO3)2]n 4. The ligands L and L′ coordinate in a monodentate fashion through the pyridine nitrogen atom to the metal centers in complexes 1 and 3. However, complexes 2 and 4 are coordination polymers in which the corresponding ligands (L and L′) act as bridging bidentate between metal centers to form 1D double chains. All the four complexes form networks through coordination polymerization and/or hydrogen bonding.

Reaction of Co(ClO4)2 · 6H2O with N,N-diisopropylisonicotinamide (L) has yielded a 1-D coordination polymer [{Co(L)2(H2O)2}(ClO4)2(CH3COCH3)2(H2O)2] n (1). Complex 1 has been characterized by infrared (IR) and UV-Vis spectroscopies, thermal analysis, and single crystal X-ray diffraction techniques. The structure has alternate arrangement of parallel 1-D cationic metal-ligand chains and H-bonded anionic chains containing perchlorate, acetone and water in the lattice. Further hydrogen bonding among both chains leads to formation of 2-D networks along almost perpendicular planes. Interpenetrations of such perpendicular 2-D sheets create a 3-D supramolecular structure.

4 pages, 3 figures, 1 table.-- PMID: 20383019 [PubMed], LytC, one of the major autolysins from the human pathogen Streptococcus pneumoniae, has been crystallized as needles by the hanging-drop technique using 10%(w/v) PEG 3350 as precipitant and 10 mM HEPES pH 7.5. LytC crystals were quickly soaked in mother liquor containing 2 mM of the complex Gd-HPDO3A to produce derivatized crystals (LytC(Gd-HPDO3A)). Both native LytC and isomorphous LytC(Gd-HPDO3A) crystals were flash-cooled in a nitrogen flow at 120 K prior to X-ray data collection using an in-house Enraf-Nonius rotating-anode generator (lambda = 1.5418 A) and a MAR345 imaging-plate detector. In both cases, good-quality diffraction patterns were obtained at high resolution. LytC(Gd-HPDO3A) crystals allowed the collection of a SAD X-ray data set to 2.6 A resolution indexed in terms of a P2(1) monoclinic unit cell with parameters a = 59.37, b = 67.16, c = 78.85 A, beta = 105.69 degrees . The anomalous Patterson map allowed the identification of one heavy-atom binding site, which was sufficient for the calculation of an interpretable anomalous map at 2.6 A resolution., This work was supported by grants from the Spanish Ministry of Science and Technology (BFU2008-01711, SAF2006-00390 and the Factoría de Cristalización from the CONSOLIDER-INGENIO 2010 program), EU-CP223111 (CAREPNEUMO, European Union). CIBER de Enfermedades Respiratorias is an initiative of Spanish Instituto de Salud Carlos III. IP-D and SR were granted I3P-CSIC and FPI fellowships, respectively.

The plant SOS2 family of protein kinases and their interacting activators, the SOS3 family of calcium-binding proteins, function together in decoding calcium signals elicited by different environmental stimuli. SOS2 is activated by Ca-SOS3 and subsequently phosphorylates the ion transporter SOS1 to bring about cellular ion homeostasis under salt stress. In addition to possessing the kinase activity, members of the SOS2 family of protein kinases can bind to protein phosphatase 2Cs. The crystal structure of the binary complex of Ca-SOS3 with the C-terminal regulatory moiety of SOS2 resolves central questions regarding the dual function of SOS2 as a kinase and a phosphatase-binding protein. A comparison with the structure of unbound SOS3 reveals the basis of the molecular function of this family of kinases and their interacting calcium sensors. Furthermore, our study suggests that the structure of the phosphatase-interaction domain of SOS2 defines a scaffold module conserved from yeast to human.

Presentación realizada por el Dr. Martín Martínez Ripoll, del Instituto de Química-Física Rocasolano del CSIC con motivo de las VI Jornadas de El CSIC y la Fundación BBVA en la Escuela celebradas en Málaga en octubre de 2015. Documento PDF de 78 páginas con material gráfico y vídeos embebidos., En las VI Jornadas de El CSIC y la Fundación BBVA en la Escuela, y con motivo del Año Internacional de la Luz, se ha hecho un recorrido por la historia de la óptica. Pues bien, en dicho contexto se ha contribuido con una charla divulgativa en donde se ponía de manifiesto el descubrimiento de la “luz X” (los rayos X), y cómo éstos son capaces de dispersarse y difractarse a través de “las rendijas” que proporcionan los cristales (la materia ordenada). Gracias a la interacción entre los rayos X y los cristales hoy conocemos la estructura íntima de la materia, es decir, el modo en el que se ordenan átomos y moléculas, determinando sus propiedades, tanto para la materia viva o inanimada. De esta manera hemos podido conocer el mundo de lo diminuto, de los átomos y molécula, averiguando cómo son, por ejemplo, las hormonas, los ácidos nucleicos, los enzimas, las proteínas y los virus, “viéndolos” en tres dimensiones y en detalle, a nivel atómico. Los estudios a través de la luz del cristal nos proporcionaron los secretos estructurales del ADN, el llamado código genético. Podemos aumentar la resistencia de las plantas frente al deterioro medioambiental. Somos capaces de modificar o inhibir enzimas implicados en procesos fundamentales de la vida e importantes para mecanismos de señalización que ocurren en el interior de nuestras células, como el cáncer. Gracias al conocimiento de la estructura del ribosoma, la mayor fábrica de proteínas de las células, podemos entender el funcionamiento de los antibióticos y modificar su estructura para mejorar su eficacia. De la estructura de enzimas, producidos por ciertos virus, hemos aprendido cómo combatir bacterias con alta resistencia a antibióticos, y ya somos capaces de desentrañar las sutiles maquinarias de defensa que han desarrollado estos gérmenes, con lo que ya no es un sueño pensar que podremos combatirlos con herramientas eficaces y alternativas a los antibióticos., CSIC, Fundación BBVA

A new series of tripodal receptors bearing imine linkages have been prepared in high yields, by a single step condensation reaction between tripodal aromatic amines and aldehydes, using zinc perchlorate as a template. The template cation leaves the pseudo cavity after the Schiff base condensation to give metal free multidentate ligands. These products have been characterized by 1H, 13C NMR, IR, elemental analysis, UV–vis absorption spectroscopy and X-ray crystallographic studies. It has been seen that the presence of a coordinating atom such as O, S, and N at position-2 with respect to the carbonyl group, is mandatory for the reaction to proceed. The template reaction has been also successfully employed to synthesize a lariat type coronand by reacting the tripodal amine with a dialdehyde.

disponible en: http://www.xtal.iqfr.csic.es/publications/jbc2005.pdf, LSL is a lectin produced by the parasitic mushroom Laetiporus sulphureus, which exhibits hemolytic and hemagglutinating activities. Here, we report the crystal structure of LSL refined to 2.6-Å resolution determined by the single isomorphous replacement method with the anomalous scatter (SIRAS) signal of a platinum derivative. The structure reveals that LSL is hexameric, which was also shown by analytical ultracentrifugation. The monomeric protein (35 kDa) consists of two distinct modules: an N-terminal lectin module and a pore-forming module. The lectin module has a -trefoil scaffold that bears structural similarities to those present in toxins known to interact with galactose-related carbohydrates such as the hemagglutinin component (HA1) of the progenitor toxin from Clostridium botulinum, abrin, and ricin. On the other hand, the C-terminal pore-forming module (composed of domains 2 and 3) exhibits three-dimensional structural resemblances with domains 3 and 4 of the -pore-forming toxin aerolysin from the Gram-negative bacterium Aeromonas hydrophila, and domains 2 and 3 from the -toxin from Clostridium perfringens. This finding reveals the existence of common structural elements within the aerolysin-like family of toxins that could be directly involved in membrane- pore formation. The crystal structures of the complexes of LSL with lactose and N-acetyllactosamine reveal two dissacharide-binding sites per subunit and permits the identification of critical residues involved in sugar binding., This work was supported by Ministerio de Educación y Ciencia Grant BFU2004-01554/BMC (to J. M. M., M. M.-R., and J. A. H.) and National Institutes of Health Research Grant GM29477 (to I. J. G.). The costs of publication of this article were defrayed in part by the payment of page charges.

Readily available p-tolylsulfinimines undergo highly stereoselective [3 + 2] cycloadditions with azomethine ylides generated from α -iminoesters and LDA to produce N-sulfinylimidazolidines. In the presence of Lewis acids, p-tolylsulfinimines react with glycine iminoester enolates to produce N-sulfinylimidazolidines, after cyclization of open chain intermediates. These mechanistically diverse processes take place with excellent regio-, stereo-, and facial selectivities, and the latter is opposite to most known reactions involving sulfinimines. Some of the resulting imidazolidines have been transformed into examples of a novel class of nonsymmetrical vicinal diamines using reductive and/or hydrolytic protocols.

Sticholysin II (StnII) is a pore-forming protein (PFP) produced by the sea anemone Stichodactyla helianthus . We found out that StnII exists in a monomeric soluble state but forms tetramers in the presence of a lipidic interface. Both structures have been independently determined at 1.7 A and 18 A resolution, respectively, by using X-ray crystallography and electron microscopy of two-dimensional crystals. Besides, the structure of soluble StnII complexed with phosphocholine, determined at 2.4 A resolution, reveals a phospholipid headgroup binding site, which is located in a region with an unusually high abundance of aromatic residues. Fitting of the atomic model into the electron microscopy density envelope suggests that while the β sandwich structure of the protein remains intact upon oligomerization, the N-terminal region and a flexible and highly basic loop undergo significant conformational changes. These results provide the structural basis for the membrane recognition step of actinoporins and unexpected insights into the oligomerization step.

11 p.-5 fig.-2 tab., Pneumococcal bacteriophage-encoded lysins are modular choline binding proteins that have been shown to act as enzymatic antimicrobial agents (enzybiotics) against streptococcal infections. Here we present the crystal structures of the free and choline bound states of the Cpl-1 lysin, encoded by the pneumococcal phage Cp-1. While the catalytic module displays an irregular (β/α)5β3 barrel, the cell wall-anchoring module is formed by six similar choline binding repeats (ChBrs), arranged into two different structural regions: a left-handed superhelical domain configuring two choline binding sites, and a β sheet domain that contributes in bringing together the whole structure. Crystallographic and site-directed mutagenesis studies allow us to propose a general catalytic mechanism for the whole glycoside hydrolase family 25. Our work provides the first complete structure of a member of the large family of choline binding proteins and reveals that ChBrs are versatile elements able to tune the evolution and specificity of the pneumococcal surface proteins., This work was supported by grants BIO2000-1307 and BIO2002-02887 from Dirección General de Investigación and by grant of Contrato-Programa de Grupos Estratégicos (BMC2000-1002) de la Comunidad Autónoma de Madrid.

A new procedure for the asymmetric synthesis of imidazolidines and vicinal diamines is reported. The 1,3-dipolar cycloaddition between nonracemic p-tolylsulfinimines and azomethine ylides generated in situ from alpha-iminoesters and LDA produces N-sulfinylimidazolidines with a high degree of stereocontrol. In contrast, the presence of Lewis acids promotes formation of the cycloadducts through a highly diastereoselective process with opposite stereochemistry. Subsequent transformations of the imidazolidines including oxidative, reductive, and hydrolytic processes that provide easy access to vicinal diaminoalcohols have been explored. Among these, reductive cleavage of the aminal with LiAlH4 is an extremely efficient and general reaction for the synthesis of enantiopure N-sulfinyl-N'-benzyldiaminoalcohols

Li + -sensitive/Mg 2+ -dependent phosphatases have attracted considerable attention since they have been proposed as targets for lithium therapy in the treatment of manic-depressive patients. The members of this enzyme superfamily display low levels of sequence identity while possessing a common fold and active site. Extensive structural and biochemical data demonstrate the direct involvement of two metal ions in catalysis, and show that lithium exerts its inhibitory action by blocking the products at the active site. By exploiting the different inhibitory properties of magnesium and calcium, we have been able to solve the X-ray structures of the Li + -sensitive/Mg 2+ -dependent 3′-phosphoadenosine-5′-phosphatase in complex with its substrate and with its products. The structural comparison of these complexes provides a 3D picture of the different stages of the catalytic cycle. This gives new insights into the understanding of the biological function of this group of enzymes and their lithium inhibition, and should assist in the design of improved inhibitors of therapeutic value.

10 páginas.-- 6 figuras.-- 77 referencias.-- This article contains supporting information online at http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1407610111/-/DCSupplemental, Data deposition: The atomic coordinates have been deposited in the Protein Data Bank (PDB), www.pdb.org (PDB ID codes 4CZT, 4CZU, and 4D28)., © 2014, National Academy of Sciences. All rights reserved. Plant cells have developed specific protective molecular machinery against environmental stresses. The family of CBL-interacting protein kinases (CIPK) and their interacting activators, the calcium sensors calcineurin B-like (CBLs), work together to decode calcium signals elicited by stress situations. The molecular basis of biological activation of CIPKs relies on the calcium-dependent interaction of a self-inhibitory NAF motif with a particular CBL, the phosphorylation of the activation loop by upstream kinases, and the subsequent phosphorylation of the CBL by the CIPK. We present the crystal structures of the NAF-truncated and pseudophosphorylated kinase domains of CIPK23 and CIPK24/SOS2. In addition, we provide biochemical data showing that although CIPK23 is intrinsically inactive and requires an external stimulation, CIPK24/SOS2 displays basal activity. This data correlates well with the observed conformation of the respective activation loops: Although the loop of CIPK23 is folded into a well-ordered structure that blocks the active site access to substrates, the loop of CIPK24/SOS2 protrudes out of the active site and allows catalysis. These structures together with biochemical and biophysical data show that CIPK kinase activity necessarily requires the coordinated releases of the activation loop from the active site and of the NAF motif from the nucleotide-binding site. Taken all together, we postulate the basis for a conserved calcium-dependent NAF-mediated regulation of CIPKs and a variable regulation by upstream kinases., A.A. thanks Dr. Douglas Vinson Laurents for critical reading of the manuscript, and the European Syncrotron Radiation Facility (beamlines ID14-4 and ID23-2) and PETRAIII (beamline P13, BIOSTRUCTX_3100.5) for the access to the synchrotron radiation source. This work was funded by Ministerio de Economía y Competitividad Grants BFU2011-25384 and CSD2006-00015 (to A.A.), BIO2011-28184-C02-02 (toM.J.S.-B.), and BIO2012-36533 (to F.J.Q.), which was cofinanced by the European Regional Development Fund, and Comunidad de Madrid Grant S2010/BMD-2457 (to A.A.). A.C.-S. is supported by a Formación de Personal Investigador Predoctoral Fellowship, and M.J.S.-B. is supported by Ramón y Cajal Contract RYC-2008-03449 from MINECO.

43 p.-5 fig., Separation of daughter cells during bacterial cell division requires splitting of the septal cross wall by peptidoglycan hydrolases. In Streptococcus pneumoniae, PcsB is predicted to perform this operation. Recent evidence shows that PcsB is recruited to the septum by the transmembrane FtsEX complex, and that this complex is required for cell division. However, PcsB lacks detectable catalytic activity in vitro, and while it has been proposed that FtsEX activates PcsB, evidence for this is lacking. Here we demonstrate that PcsB has muralytic activity, and report the crystal structure of full-length PcsB. The protein adopts a dimeric structure in which the V-shaped coiled–coil (CC) domain of each monomer acts as a pair of molecular tweezers locking the catalytic domain of each dimeric partner in an inactive configuration. This suggests that the release of the catalytic domains likely requires an ATP-driven conformational change in the FtsEX complex, conveyed towards the catalytic domains through coordinated movements of the CC domain., This work was supported by grants BFU2011-25326 and S2010/BMD-2457 and grants from the Research Council of Norway.

A series of esters derived from (±) 3-hydroxy-1-azabicyclo[2.2.2]octane-3-carboxylic acid hydrochloride were synthesised and studied by NMR spectroscopy. The combined use of 1 H– 1 H COSY, NOESY and 1 H– 13 C correlation spectra of these compounds helped in the unambiguous assignments of the bicyclic carbon and proton resonances. The crystal structure of (±) 3-diphenylacetoxy-1-azabicyclo[2.2.2]octane-3-carboxylic acid hydrochloride was determined by X-ray diffraction.

Background : The Arabidopsis thaliana HAL3 gene product encodes for an FMN-binding protein (AtHal3) that is related to plant growth and salt and osmotic tolerance. AtHal3 shows sequence homology to ScHal3, a regulatory subunit of the Saccharomyces cerevisae serine/threonine phosphatase PPz1. It has been proposed that AtHal3 and ScHal3 have similar roles in cellular physiology, as Arabidopsis transgenic plants that overexpress AtHal3 and yeast cells that overexpress ScHal3 display similar phenotypes of improved salt tolerance. The enzymatic activity of AtHal3 has not been investigated. However, the AtHal3 sequence is homologous to that of EpiD, a flavoprotein from Staphylococcus epidermidis that recognizes a peptidic substrate and subsequently catalyzes the α,β-dehydrogenation of its C-terminal cysteine residue. Results : The X-ray structure of AtHal3 at 2 A resolution reveals that the biological unit is a trimer. Each protomer adopts an α/β Rossmann fold consisting of a six-stranded parallel β sheet flanked by two layers of α helices. The FMN-binding site of AtHal3 contains all the structural requirements of the flavoenzymes that catalyze dehydrogenation reactions. Comparison of the amino acid sequences of AtHal3, ScHal3 and EpiD reveals that a significant number of residues involved in trimer formation, the active site, and FMN binding are conserved. This observation suggests that ScHal3 and EpiD might also be trimers, having a similar structure and function to AtHal3. Conclusions: Structural comparisons of AtHal3 with other FMN-binding proteins show that AtHal3 defines a new subgroup of this protein family that is involved in signal transduction. Analysis of the structure of AtHal3 indicates that this protein is designed to interact with another cellular component and to subsequently catalyze the α,β-dehydrogenation of a peptidyl cysteine. Structural data from AtHal3, together with physiological and biochemical information from ScHal3 and EpiD, allow us to propose a model for the recognition and regulation of AtHal3/ScHal3 cellular partners.

The ligands 4,6-bis(pyrazol-1-yl)pyrimidine (bpzpm) and 4,6-bis(4-methylpyrazol-1-yl)pyrimidine (Me−bpzpm) were synthesized and their reactions with some palladium derivatives explored. Mononuclear or dinuclear neutral or cationic complexes were obtained by reaction of the ligands with 1 or 2 equiv of Pd(C6XF4)2(cod) (cod = 1,5-cyclooctadiene; X = F, H) or the palladium fragment [Pd(η3-2-Me-C3H4)(S)2]+ (S = acetone). The reaction of the dinuclear derivatives with 1 equiv of the respective free ligand immediately led to the regeneration of the mononuclear complexes. Except in the case of the synthesis of [{Pd(C6HF4)2}{Pd(C6F5)2}(bpzpm)], where two similar metallic groups are present, all attempts to obtain dinuclear asymmetric complexes with two different palladium fragments failed. Instead, the dinuclear symmetric complexes were formed. This result could be considered as an example of molecular recognition with the ligand acting as a ditopic receptor. This behavior is comparable to chemical symbiosis but ...

The regioselective acylation of phenylalkanediols catalysed by porcine pancreatic lipase (PPL) was the reaction used for modelling different areas in the active site of the enzyme. With this aim, different racemic or prochiral (1,n)-diols, with n ranging from 2 to 6 were resolved via transesterification with vinyl acetate, and the results were explained according to microcrystalline enzyme structure. Thus, we describe a logical model for explaining the enzyme regio and stereoselectivity, based on three residues of the active site (Ser153, Phe216 and His264) which turned out to be crucial for the substrate binding and transformation.

A new and convenient route for preparation of [Ru(trpy)(H2O)3]2+ involving reductive cleavage of the corresponding oxo dimers has been established. Furthermore, new complexes bearing the tridentate facial ligand tpm (tris(1-pyrazolyl)methane) and the tridentate meridional ligand trpy (2,2′:6′,2″-terpyridine) have been prepared from the corresponding [RuIIL(H2O)3]2+ (L=tpm, trpy) precursors. The complexes obtained with general formula [RuIILL′]2+ (L=tpm, L′=py3, py2H2O; L=trpy, L′=trpy, py3, Cl3) have been spectroscopically and electrochemically characterised and the structure of [Ru(tpm)(py)3](PF6)2 and of [RuCl3(trpy)] determined by means of X-ray crystallography.

The increasing development of the biotechnology industry demands the design of enzymes suitable to be used in conditions that often require broad resistance against adverse conditions. β-glucosidase A from Bacillus polymyxa is an interesting model for studies of protein engineering. This is a well-characterized enzyme, belonging to glycosyl hydrolase family 1. Its natural substrate is cellobiose, but is also active against various artificial substrates. In its native state has an octameric structure. Its subunit conserves the general (α/β)8 barrel topology of its family, with the active site being in a cavity defined along the axis of the barrel. Using random-mutagenesis, we have identified several mutations enhancing its stability and it was found that one them, the E96K substitution, involved structural changes. The crystal structure of this mutant has been determined by X-ray diffraction and compared with the native structure. The only difference founded between both structures is a new ion pair linking Lys96 introduced at the N-terminus of helix α2, to Asp28, located in one of the loops surrounding the active-site cavity. The new ion pair binds two segments of the chain that are distant in sequence and, therefore, this favorable interaction must exert a determinant influence in stabilizing the tertiary structure. Furthermore, analysis of the crystallographic isotropic temperature factors reveals that, as a direct consequence of the introduced ion pair, an unexpected decreased mobility of secondary structure units of the barrel which are proximal to the site of mutation is observed. However, this effect is observed only in the surrounding of one of the partners forming the salt bridge and not around the other. These results show that far-reaching effects can be achieved by a single amino acid replacement within the protein structure. Consequently, the identification and combination of a few single substitutions affecting stability may be sufficient to obtain a highly resistant enzyme, suitable to be used under extreme conditions. Proteins 33:567–576, 1998. © 1998 Wiley-Liss, Inc.

The (aminoferrocenyl)phosphine ligand 1-diphenylphosphino-2,1‘-(1-dimethylaminopropanediyl)ferrocene, 1, was used to synthesize new palladium(0) and -(II) complexes. The reaction of Pd2(dba)3·CHCl3...

New Schiff bases from benzil with semicarbazide and thiosemicarbazide are reported. An open chain molecule, benzilbissemicarbazone 1 was prepared in presence of lithium hydroxide. A cycle 6-methoxy-1,6-diphenyl-4-thio-3,4,5,6-tetrahydro-2,3,5-triazine 7 was obtained from thiosemicarbazide. A cyclic molecule, 1,6-diphenyl-4-oxo-3,4,5,6-tetrahydro-2,3,5-triazine 4 was produced from the recrystallization of 3 in chloroform. A new macrocyclic complex 8 was isolated from the open chain 6 in the presence of iron (III) chloride hexahydrated. Compounds 1, 2 convert into the cyclic 3 heated under reflux. In addition, we have got an iron complex 5 of 1 using the compound 2 as precursor. The crystal structure of 7 was obtained by single crystal X-Ray diffraction.

Reaction of readily available macrocyclic bis(carbodiimides) with nitrogen reagents such as ammonia, primary or secondary alkylamines, and α,ω-diamino compounds provided a novel class of macrocyclic bis(guanidines), which were isolated as crystalline solids in high yields (74−98%). The crystal and molecular structure of the bis(guanidine) derived from bicyclo[8.8.2]docosane 10a has been determined.

The reaction of Cp2ZrCl2 (Cp = η5-C5H5) with 2 equiv of the lithium amide derivative LiNHC6H4-o-SMe affords the new zirconium complex Cp2Zr(NHC6H4-o-SMe)2 (2). The structure of 2 has been determined by X-ray diffraction. When the reaction is carried out in an 1:1 ratio, the complex Cp2ZrCl(NHC6H4-o-SMe) (3) is generated as the major product. Reaction of “Cp*2Zr” (Cp* = η5-C5Me5) with 2-(methylmercapto)aniline yields a hydride−amide complex Cp*2ZrH(NHC6H4) (4). Reaction of complex 2 with [RhCl(COD)]2 generates complex 3 and the new rhodium amide complex Rh(NHC6H4-o-SMe)(COD), which has been also directly synthesized by reacting [RhCl(COD)]2 with LiNHC6H4-o-SMe. Thermolysis of complex 6, at 100 °C, produces to a new rhodium thiolate complex [Rh(μ-SC6H4-o-NHMe)(COD)]2 (5). Its structure has been determined by X-ray diffraction methods. Reaction of [IrCl(COD)]2 with LiNHC6H4-o-SMe gives the iridium(III) complex Ir(Me)(SC6H4NH)(COD) (7) by oxidative addition of the S−Me bond.

Family 1 glycosyl hydrolases are a very relevant group of enzymes because of the diversity of biological roles in which they are involved, and their generalized occurrence in all sorts of living organisms. The biological plasticity of these enzymes is a consequence of the variety of beta-glycosidic substrates that they can hydrolyze: disaccharides such as cellobiose and lactose, phosphorylated disaccharides, cyanogenic glycosides, etc. The crystal structure of BglA, a member of the family, has been determined in the native state and complexed with gluconate ligand, at 2.4 A and 2.3 A resolution, respectively. The subunits of the octameric enzyme display the (alpha/beta)8 barrel structural fold previously reported for other family 1 enzymes. However, significant structural differences have been encountered in the loops surrounding the active-center cavity. These differences make a wide and extended cavity in BglA, which seems to be able to accommodate substrates longer than cellobiose, its natural substrate. Furthermore, a third sub-site is encountered, which might have some connection with the transglycosylating activity associated to this enzyme and its certain activity against beta-1,4 oligosaccharides composed of more than two units of glucose. The particular geometry of the cavity which contains the active center of BglA must therefore account for both, hydrolytic and transglycosylating activities. A potent and well known inhibitor of different glycosidases, D-glucono-1,5-lactone, was used in an attempt to define interactions of the substrate with specific protein residues. Although the lactone has transformed into gluconate under crystallizing conditions, the open species still binds the enzyme, the conformation of its chain mimicking the true inhibitor. From the analysis of the enzyme-ligand hydrogen bonding interactions, a detailed picture of the active center can be drawn, for a family 1 enzyme. In this way, Gln20, His121, Tyr296, Glu405 and Trp406 are identified as determinant residues in the recognition of the substrate. In particular, two bidentate hydrogen bonds made by Gln20 and Glu405, could conform the structural explanation for the ability of most members of the family for displaying both, glucosidase and galactosidase activity.

The crystal packing modes of nitrobenzene derivatives, compounds classified as BCLASS = 15 by the Cambridge Structural Database (CSD), have been analysed. Several packing modes have been observed, although two of them, the so-called stacks and pseudo-herringbone, appear as the most populated ones. In 28.4% of the 169 structures that fulfilled the conditions of the search, the molecules are packed to form columns, with the aromatic planes almost parallel. Different ways of stacking within the columns and the way in which these columns pack together to give the whole crystal have been analysed.

Nitrobenzene derivatives pack in two main motifs: stacks [see André , Foces-Foces, Cano & Martinez-Ripoll (1997). Acta Cryst. B53, 984–995] and `pseudo- herringbone' together account for some 61.5% of the structures classified as BCLASS = 15 by the Cambridge Structural Database. Several geometrical parameters allow the classification of the `pseudo-herringbone' category into four main motifs. Weak interactions appear to play an important role in this packing mode.

The perfluorothiolate dinuclear compounds [Rh( μ -SC 6 F 5 )(COD)[ 2 1 and [Rh( μ -SC 6 F 5 )(CO) 2 [ 2 2 react with PPh 3 to give monomeric and dimeric complexes, the particular product depending upon the PR 3 /Rh ratio and reaction conditions. Reaction of 2 with 2 moles of PPh 3 renders cis - 7 and trans -[Rh( μ -SC 6 F 5 )((CO)(PPh 3 )[ 2 8 , while with 4 moles of PPh 3 trans [Rh(SC 6 F 5 )(CO)(PPh 3 ) 2 [ 10a is obtained. This latter product can otherwise be prepared by Cl metathesis from trans -[RhCl(CO(PPh 3 ) 2 [ in toluene. This same reaction in dichloromethane however yields the cis isomer 10b . When a larger excess of PPh 3 is used, a mixture of compounds 11a and 11b is formed. An X-ray crystal structure study shows trans [Rh(SC 6 F 5 )(CO)(PPh 3 ) 2 [ to exit as two polymorphs. 11a crystallises in the space group P2 1 /n of the monoclinic system with a = 12.489(1), b = 15.430(5), c = 19.719(1) A, α = γ = 90, β = 92.84(1)°, and 11b is triclinic, space group P1¯ with a = 9.764(2), b = 12.197(6), c = 17.880 A, α = 100.18(5), β = 101.92(2), γ = 113.61(2)°. Both PPh 3 ligands are mutually trans and the difference in v (CO) stretching frequencies 1989 and 1939 cm −1 , can be explained in terms of o-phenyl H…CO interactions in the latter. The [Rh( μ -SC 6 F 5 )(COD)[ 2 1 and [Rh( μ -SC 6 F 5 )(CO) 2 [ 2 2 /nPPh 3 systems have been studied as catalyst precursors for the hydroformylation of 1-heptene in toluene at 30 bar and 343 K. Selectivity towards the linear aldehyde is enhanced when dimeric complexes are used.

8 pags, 4 figs, 2 tabs, Fosfomycin targets the first step of peptidoglycan biosynthesis in Streptococcus pneumoniae catalyzed by UDP-N-acetylglucosamine enolpyruvyltransferase (MurA1). We investigated whether heteroresistance to fosfomycin occurs in S. pneumoniae.We found that of 11 strains tested, all but 1 (Hungary19A) displayed heteroresistance and that deletion of murA1 abolished heteroresistance. Hungary19A differs from the other strains by a single amino acid substitution in MurA1 (Ala364Thr). To test whether this substitution is responsible for the lack of heteroresistance, it was introduced into strain D39. The heteroresistance phenotype of strain D39 was not changed. Furthermore, no relevant structural differences between the MurA1 crystal structures of heteroresistant strain D39 and nonheteroresistant strain Hungary19A were found. Our results reveal that heteroresistance to fosfomycin is the predominant phenotype of S. pneumoniae and that MurA1 is required for heteroresistance to fosfomycin but is not the only factor involved. The findings provide a caveat for any future use of fosfomycin in the treatment of pneumococcal infections. Copyright © 2013, American Society for Microbiology. All Rights Reserved., This study was supported by grants from the Spanish Ministry of Economy and Competitiveness (BFU2011-25326), the Madrid Regional Government (S2010/BMD-2457), and the Swiss Centre for Antibiotic Resistance

The Arabidopsis SOS2 family of twenty-six protein kinases (CIPKs), their interacting activators, the SOS3 family of ten calcium-binding proteins (CBLs) and protein phosphatases type 2C (PP2C), function together in decoding calcium signals elicited by different environmental stimuli. Biochemical data suggest that stable CBL-CIPK or CIPK-PP2C complexes may be regulating the activity of various substrates controlling ion homeostasis. The available structural information provides a general regulatory mechanism in which calcium perception by CBLs and kinase activation is coupled. The structural basis of this molecular mechanism and the specificity of the network is reviewed and discussed in detail., This work was funded by grants BIO2011-28184-C02-02 to M.J.S.-B. and BFU2011-25384 to A.A. M.J.S.-B. was supported by a Ramón y Cajal contract RYC-2008-03449. Our apologies to those whose work could not be included due to space constraints.

The mixed hydroxo-bromo bridged complex [{Pd(C6H4CH2NMe2)}2(μ-Br)(μ-OH)] (1) (C6H4CH2NMe2 = 2-[(dimethyl-amino)methyl]phenyl) has been prepared by addition of one equivalent of NBu4OH to [{Pd(C6H4CH2NMe2)(μ-O2CMe)}2] in acetone-water solution, followed by addition of one equivalent of LiBr. Complex 1 reacts with arylamines or thiols in 1:1 mole ratio to yield the corresponding amido- or thiolato-bromo complexes [{Pd(C6H4CH2NMe2)}2(μ-Br)(μ-NHR)] (R = C6H5 (2), p-MeOC6H4 (3), p-MeOC6H4 (4)) or [{Pd(C6H4CH2NMe2)}2(μ-Br)(μ-SR)] (R = Et (5). 1Bu (6), C6H5 (7), p-MeC6H4 (8)). The 1H NMR data indicate a cis arrangement of the C6H4CH2NMe2 ligands. The crystal structure of compound 1 has been determined by X-ray diffraction. It crystallizes in the orthorhombic space group Pbca with a = 12.445(3), b = 18.029(3), c = 17.436(3) A . Final R = 0.039 and Rn = 0.040 based on 2692 reflections.

The diastereoselectivity of the nucleophilic epoxidation of vinyl sulfoxides bearing oxygenated substituents at allylic positions, 1–4, with MOO-t-Bu (M = Na, K) is primarily controlled by the chiral sulfur atom.

2,3-Benzo-1,4-dioxa-7,11,15-triazacycloheptadec-2-ene-6,16-dione, C16H23N3O4, is a 17-membered ring with an envelope conformation in which amide N and ether O atoms form one plane and the amine N atom lies on the flap. 2,3-Benzo-1,4-dioxa-7,10,13-triazacyclopentadec-2-ene-6,14-dione–water (1/2), C14H19N3O4.2H2O, has a 15-membered ring with all the donor atoms in an approximately planar arrangement. The amide groups of this macrocycle are hydrogen bonded to the water molecules. It appears that the availability of the unsubstituted amine N atom is crucial for the extraction and transport of Pb2+ ions. Substitution of a side arm on the amine N atom significantly alters the coordination ability of this N atom in the 17-membered ring and decreases the extraction and transport ability of the macrocycle.

In the title complex, [Ca(C6H15NO3)2](C7H3N2O6)2, the Ca2+ ion is sandwiched between two triethanolamine ligands, each of them coordinating through all four potential donor sites. The coordination polyhedron is distorted cubic. The 3,5-dinitrobenzoate counter anions do not interact directly with the cation but are hydrogen bonded to the hydroxyl groups of the triethanolamine ligands.

The title dimeric compound, bis(μ-3,5-dinitrobenzoato-O:O')bis[(triethylene glycol-O,O',O”,O”')calcium(II)] bis(3,5-dinitrobenzoate) dihydrate, {[Ca(C7H3N2O6)(C6H14O4)(H2O)](C7H3N2O6).H2O}2, has seven-coordinate Ca centres with distorted pentagonal bipyramidal geometry. Four O atoms in the coordination sphere belong to the triethylene glycol ligand, one belongs to the water molecule and the two final O atoms are from two different symmetry-related carboxylate groups belonging to two symmetry-related 3,5-dinitrobenzoate anions. anions. The second dinitrobenzoate anion in the asymmetric unit does not participate in coordination, but is involved in hydrogen bonding to the hydroxyl groups of the triethylene glycol ligand.

The salt-tolerance gene SOS3 (salt overly sensitive 3) of Arabidopsis thaliana encodes a calcium-binding protein that is able to sense the cytosolic calcium signal elicited by salt stress. SOS3 activates the SOS2 protein kinase, which activates various ion transporters. SOS3 was cloned into a plasmid and expressed in Escherichia coli, allowing purification of the protein to homogeneity. Two crystals with different additive contents were grown. Both diffract to 3.2 A resolution and belong to space group I4(1), with unit-cell parameters a = 93.65, c = 80.08 A and a = 91.79, c = 85.78 A, respectively. A promising molecular-replacement solution has been found using neuronal calcium-sensor 1 as the search model. Interestingly, no solution was found using AtCBL2 (A. thaliana calcineurin B-like protein) structure as a search model, although this protein belongs to the same family and displays 50% sequence identity.

A series of amides derived from 3,7-dimethyl-3,7-diazabicyclo [3.3.1] nonan-9-amine have been synthesized and examined by 1 H and 13 C NMR spectroscopy and the crystal structure of 9-(2,4,6-trichlorobenzamido)-3,7-dimethyl-3,7-diazabicyclo[3.3.1] nonane hydrochloride ( 4a ·HCl) has been determined by X-ray diffraction. These compounds adopt an almost perfect chair-chair conformation with the NCH 3 groups in equatorial position. This conformation is nearly the same as that observed for compound 4a in the solid state. From binding studies of compounds 4a–c , compound 4b demonstrated the ability to efficiently displace [ 3 H]GR65630 bound to bovine brain area postrema membranes to an extent comparable to MDL 72222. In the von Bezold-Jarish reflex, compound 4b showed significant results at a dose of 25 mg Kg −1 . It is shown for the first time that a series of compounds with a bispidine skeleton linked through an amide moiety to several aromatic rings, shows 5-HT 3 antagonistic profiles.

The title complex, bis(2,4-dinitrophenolato-O,O 2 )-(2,2',2''-nitrilotriethanol-N,O,O',O'')calcium(II), [Ca(C 6 H 3 N 2 O 5 ) 2 (C 6 H 15 NO 3 )], is monomeric and the Ca 2+ ion is eight-coordinate. Both dinitrophenolate ligands coordinate to the metal ion by their phenolic O atoms and one O atom of the ortho-nitro group. Ca is further coordinated by all the O atoms and the N atom of triethanolamine, the O atoms of which are also hydrogen-bond donors. The phenolic O atoms and one O atom of a para-nitro group take part in intermolecular hydrogen bonding.

Synthesis and reactivity analysis of the 1,2-dihydrocarbazol-4(3H)-one, and the N-methyl, N-tosyl and 2,2-dimethyl derivatives have been carried out. Molecular structures of the N-methyl and N-tosyl derivatives have been analyzed by X-ray diffraction. Crystals of the N-methyl derivative are monoclinic, space group P21/c,a=8.868(1),b=16.652(1),c=7.5440(4) A, β=113.657(3). Crystals of the N-tosyl derivative are monoclinic, P21/c,a=12.0016(3),b=8.9178(2),c=16.0485(4) A, β=104.372(2). An extended conjugation from the carbonyl group to the nitrogen atom and an envelope conformation for the common cyclohexenone fragment are evident in both cases. Oximation and Beckmann rearrangement, and etherification of the carbonyl group is reported.

The structure of the product obtained by reacting phenylhydrazine, p-chlorophenylhydrazine and hydrazine itself with dehydroacetic acid has been established by a combined use of X-ray crystallography and NMR (1H and 13C) spectroscopy. The X-ray structure of 1-phenyl-3-methyl-4(1-phenyl-3-methyl-1H-pyrazol-5-yl)-2H-3-pyrazolin-5-one1d has been determined. The compound crystallizes in the space group P 2 1 a [C20H18N4O, a = 11.801(2), b = 7.911(1), c = 18.363(2) A, α = 90.00°, β = 100.04°, γ = 90.00°, Z = 4]. The structure corresponds to the NH-tautomer of the pyrazolinone moiety; the angle of twist corresponding to pyrazole rings, defined as C1-C2-C4-C5, is −119.1(7)°. NMR spectrum allows to estimate the tautomeric equilibrium constant in solution and in the solid state. The X-ray structure of compound 1 (NH-tautomer) was determined and compared with NMR results (solution and solid state).

The crystal structure of a new dihydrogendecavanadate(V) of n-hexylammonium has been determined by means of X-ray diffraction data. Empirical bond length/bond number calculations have located the protonation sites in two triply-linked oxygen atoms which reinforce theoretical results of relative basicities of the oxygen sites in decavanadate anions. The crystal structure is stabilised by electrostatic forces and an extensive network of hydrogen contacts among anions and cations. The dihydrogendecavanadate(V) anions are located on the (001) plane and are joined via hydrogen bonding, d(O ⋯ O)= 2.63 and 2.64 A, giving evidence of strong O ⋯ O interactions. Infrared spectroscopy and thermoanalytical methods have been applied in order to confirm structural properties.

The enzyme encoded by the bgIA gene of Bacillus polymyxa , a type I β-glucosidase belonging to family I of glycosyl hydrolases, has been purified to homogeneity form an Escherichia coli culture which overexpressed the gene, and crystallized. The crystals, which diffract to 3·0 A resolution, belong to the orthorhombic space group C 222 1 . The cell dimensions are a =155·4 A, b =209·4 A c =209·7 A.

The variance in the geometry of pentafluorophenyl rings bonded to metals of the fourth, fifth and sixth rows of the Periodic Table has been analyzed from the data present in the literature. The application of univariate and bivariate analysis to internal coordinates shows that the major variation corresponds to bond angles, specially to those near to the substitution. This effect (“ipso” effect) seems to be related to the Pauling's electronegativity of the metals. Multivariate analysis of these coordinates reveals the existence of three principle effects, the main one of them corresponding to the “ipso” effect and the other two being related with the thermal vibration of the molecule and with the inhomogeneity of the sample. The application of bivariate analysis to symmetry coordinates does not give any correlation between the two orthogonal components describing fully the angular variance.