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Cysteine dioxygenase (CDO) catalyzes the oxidation of L-cysteine to cysteine sulfinic acid. Deficiencies in this enzyme have been linked to autoimmune diseases and neurological disorders. The x-ray crystal structure of CDO from Mus musculus was solved to a nominal resolution of 1.75 A. The sequence is 91% identical to that of a human homolog. The structure reveals that CDO adopts the typical [beta]-barrel fold of the cupin superfamily. The NE2 atoms of His-86, -88, and -140 provide the metal binding site. The structure further revealed a covalent linkage between the side chains of Cys-93 and Tyr-157, the cysteine of which is conserved only in eukaryotic proteins. Metal analysis showed that the recombinant enzyme contained a mixture of iron, nickel, and zinc, with increased iron content associated with increased catalytic activity. Details of the predicted active site are used to present and discuss a plausible mechanism of action for the enzyme. cupin | cysteine metabolism | [O.sub.2]-activation

Here, we report that cytokine-induced (granulocyte colony-stimulating factor and IL-8) hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) mobilization is completely inhibited after low-dose (0.5 Gy) total-body irradiation (TBI). Because neutrophil granular proteases are regulatory mediators in cytokine-induced HSC/HPC mobilization, we considered a possible role for protease inhibitors in the induction of HSC/HPC mobilization. Bone marrow (BM) extracellular extracts that were obtained from murine femurs after 0.5 Gy of TBI contained an inhibitor of elastase. Also, after low-dose TBI, both Serpina1 mRNA and protein concentrations were increased in BM extracts, compared with extracts that were obtained from controls. The inhibitory activity in BM extracts of irradiated mice was reversed by addition of an Ab directed against Serpina1. To further study a possible in vivo role of Serpina1 in HSC/HPC mobilization, we administered Serpina1 before IL-8 injection. This administration resulted in an almost complete inhibition of HSC/HPC mobilization, whereas heat-inactivated Serpina1 had no effect. These results indicate that low-dose TBI inhibits cytokine-induced HSC/HPC mobilization and induces Serpina1 in the BM. Because exogenous administration of Serpina1 inhibits mobilization, we propose that radiation-induced Serpina1 is responsible for the inhibition of HSC/HPC mobilization. Also, we hypothesize that cytokine-induced HSC/HPC mobilization is determined by a critical balance between serine proteases and serine protease inhibitors. protease | protease inhibitors | bone marrow | adhesion molecules

The formation of kinetically competent adenylated intermediates is examined by observing potential isotope exchange (PIX) reaction using [[beta][gamma]-[super 18][O.sub.6]]-ATP in the presence of cysteine. The PIX analysis confirmed that the Mycobacterium smegmatis cysteine ligase (MshC) acatalyzed the formation of a kinetically competent cysteinyl-adenylate intermediate after the addition of ATP and cysteine.

The pH rate profiles are measured for several L-arginine deiminase (ADIs) from divergent organisms to define the limits of the pH range within which the His-Cys catalytic pair can operate. The results have shown that catalytic turnover commences from the active configuration of the ADI complex consisting of the Cys thiolate and His imidazolium ion.

The R163K, a variant of human thymidylate synthase (hTS), is designed and expressed, in which the inactive conformation is destabilized. The calculation have shown that the molecular electrostatic potential at cysteine 195 (Cys195) has differed between the subunits of the dimer.

The electronic structures of [Hg.sup.II], [Ni.sup.II], [Cr.sup.III] and [Mo.sup.V] complexes with cysteine are examined by sulfur K-edge X-ray absorption near-edge structure (XANES) spectroscopy and density functional theory. The well-defined structures of the selected cysteine complexes have provided a reference set for further sulfur K-edge XAS studies of bioinorganic active sites with transition metal-sulfur bonds from cysteine residues as well as more complex coordination compounds with thiolate ligands.

The reduction potential of the heme in the truncated form of human cystathionine [beta]-synthase (CBS) is determined and the reactivity of the reduced enzyme with dioxygen is examined. The results have shown that the unusual heme in CBS has represented a heretofore unrecognized potential source of cytosolic superoxide radical.

The interaction between puroindolines and lipids in the presence/absence of Pin-a which are significantly influence of tryptophan-rich loop of Pin-b are described.

A comparative study of the NMR solution structures of the apo and peptide-inhibited human rhinovirus 3C cysteine protease (serotype 14) is presented. The rmsd values for apo structures are found to be greater than that of the inhibited enzymes.

A detailed kinetic and mechanistic characterization of cysteine ligase (MshC) from Mycobacterium smegmatis carried out by using steady-state and pre-steady state approaches are described. Findings reveal that MshC catalyzes the ATP-dependent condensation of GlcN-Ins and cysteine to form Cys-GlcN-Ins and kinetic mechanism showed a Bi Uni Uni Bi Ping Pong mechanism, with ATP binding followed by cysteine binding.

The crystal structure of the C-terminal domain of 10-formyltetrahydrofolate dehydrogenase (FDH) and its complexes with oxidized and reduced forms of NADP is determined. The complex with [NADP.sup.+] has shown a covalent bond between the cysteine nucleophile and C4 of the nicotinamide ring, which is supported by the mutational and spectroscopic studies.

Natrin purified from Naja atra venom, a member of the cysteine-rich secretory proteins (CRISP) family, can induce a contractile response in the endothelium-denuded thoracic aorta of mouse which are contracted by a high-K(super +) solution. The experiments show that it could block the high-conductance calcium-activated potassium (BK(sub Ca)) channel that suggest that only a single natrin molecule is required to bind an ion channel to block BK(sub a) current.

Ervatamin C is an unusually stable cysteine protease from the medicinal plant Ervatamia coronaria belonging to the papain family. Though it cleaves denatured natural proteins with high specific activity, its activity toward some small synthetic substrates is found to be insignificant.