Search

Your search keyword '"Almo, S.C."' showing total 746 results
Start Over Author "Almo, S.C."
746 results on '"Almo, S.C."'

16. A naturally occurring mutation K220T in the pleiotropic activator PrfA of Listeria monocytogenes results in a loss of virulence due to decreasing DNA-binding affinity

Author

Velge, P., Herler, M., Johansson, J., Roche, S.M., Temoin, S., Fedorov, A.A., Gracieux, P., Almo, S.C., Goebel, W., and Cossart, P.

Subjects
Virulence (Microbiology) -- Genetic aspects, Listeria monocytogenes -- Research, Bacterial genetics -- Research, Biological sciences
Abstract

The sequencing of prfA, encoding the transcriptional regulator of virulence genes, in 26 low-virulence field Listeria monocytogenes strains showed that eight strains exhibited the same single amino-acid substitution: PrfAK220T. These strains exhibited no expression of PrfA-regulated proteins and thus no virulence. This substitution inactivated PrfA, since expression of the PrfAK220T mutant gene in an EGD[DELTA]prfA strain did not restore the haemolytic and phosphatidylcholine phospholipase C activities, in contrast to the wild-type prfA gene. The substitution of the lysine at position 220 occurred in the helix [alpha]H. However, the data showed that the PrfAK220T protein is dimerized just as well as its wild-type counterpart, but does not bind to PrfA-boxes. PrfAK220T did not form a PrfA-DNA complex in electrophoretic mobility shift assays, but low concentrations of CI complexes (PrfAK220T-RNA polymerase-DNA complex) were formed by adding RNA polymerase, suggesting that PrfA interacted with RNA polymerase in solution in the absence of DNA. Formation of some transcriptionally active complexes was confirmed by in vitro runoff transcription assays and quantitative RT-PCR. Crystallographic analyses described the structure of native PrfA and highlighted the key role of allosteric changes in the activity of PrfA and especially the role of the Lys220 in the conformation of the helix-turn-helix (HTH) motif.

Published
2007

17. The structure of nonvertebrate actin: implications for the ATP hydrolytic mechanism

Author

Vorobiev, S., Strokopytov, B., Drubin, D.G., Frieden, C., Ono, S., Condeelis, J., Rubenstein, P.A., and Almo, S.C.

Subjects
Muscle proteins -- Research, Muscle proteins -- Physiological aspects, Science and technology, National Academy of Sciences -- Research
Abstract

The structures of Saccharomyces cerevisiae, Dictyostelium, and Caenorhabditis elegans actin bound to gelsolin segment-1 have been solved and refined at resolutions between 1.9 and 1.75 [Angstrom]. These structures reveal several features relevant to the ATP hydrolytic mechanism, including identification of the nucleophilic water and the roles of Gin-137 and His-161 in positioning and activating the catalytic water, respectively. The involvement of these residues in the catalytic mechanism is consistent with yeast genetics studies. This work highlights both structural and mechanistic similarities with the small and trimeric G proteins and restricts the types of mechanisms responsible for the considerable enhancement of ATP hydrolysis associated with actin polymerization. The conservation of functionalities involved in nucleotide binding and catalysis also provide insights into the mechanistic features of members of the family of actin-related proteins.

Published
2003

18. Transition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis

Author

Fedorov, A., Shi, W., Kicska, G., Fedorov, E., Tyler, P.C., Furneaux, R.H., Hanson, J.C., Gainsford, G.J., Larese, J.Z., Schramm, V.L., and Almo, S.C.

Subjects
Enzymes -- Structure-activity relationship, Crystals -- Structure, X-ray crystallography -- Usage, Enzyme inhibitors -- Physiological aspects, Structure-activity relationships (Biochemistry) -- Analysis, Biological sciences, Chemistry
Abstract

Crystal structure analyses of the pure bovine purine nucleoside phosphorylase enzyme and the enzyme-inhibitor complex reveal new information about the reaction coordinate of the enzyme at atomic level. The enzyme and the complex are analyzed at 0.9 and 1.5 angstrom resolution level.

Published
2001

25. Characterization of the SARS-CoV-2 S Protein: Biophysical, Biochemical, Structural, and Antigenic Analysis

Author

Herrera, N.G., primary, Morano, N.C., additional, Celikgil, A., additional, Georgiev, G.I., additional, Malonis, R., additional, Lee, J.H., additional, Tong, K., additional, Vergnolle, O., additional, Massimi, A., additional, Yen, L.Y., additional, Noble, A.J., additional, Kopylov, M., additional, Bonanno, J.B., additional, Garrett-Thompson, S.C., additional, Hayes, D.B., additional, Brenowitz, M., additional, Garforth, S.J., additional, Eng, E.T., additional, Lai, J.R., additional, and Almo, S.C., additional

Published
2020
Full Text
View/download PDF

30. Crystal structure of human WDR5

Author

Lorton, B.M., primary, Harijan, R.K., additional, Burgos, E., additional, Bonanno, J.B., additional, Almo, S.C., additional, and Shechter, D., additional

Published
2020
Full Text
View/download PDF

44. Anti-CTLA-4 therapy requires an Fc domain for efficacy

Author

Ingram, J.R., Blomberg, O.S., Rashidian, M., Ali, L., Garforth, S., Fedorov, E., Fedorov, A.A., Bonanno, J.B., Gall, C.M. le, Crowley, S., Espinosa, C., Biary, T., Keliher, E.J., Weissleder, R., Almo, S.C., Dougan, S.K., Ploegh, H.L., Dougan, M., Ingram, J.R., Blomberg, O.S., Rashidian, M., Ali, L., Garforth, S., Fedorov, E., Fedorov, A.A., Bonanno, J.B., Gall, C.M. le, Crowley, S., Espinosa, C., Biary, T., Keliher, E.J., Weissleder, R., Almo, S.C., Dougan, S.K., Ploegh, H.L., and Dougan, M.

Abstract

Item does not contain fulltext, Ipilimumab, a monoclonal antibody that recognizes cytotoxic T lymphocyte antigen (CTLA)-4, was the first approved "checkpoint"-blocking anticancer therapy. In mouse tumor models, the response to antibodies against CTLA-4 depends entirely on expression of the Fcgamma receptor (FcgammaR), which may facilitate antibody-dependent cellular phagocytosis, but the contribution of simple CTLA-4 blockade remains unknown. To understand the role of CTLA-4 blockade in the complete absence of Fc-dependent functions, we developed H11, a high-affinity alpaca heavy chain-only antibody fragment (VHH) against CTLA-4. The VHH H11 lacks an Fc portion, binds monovalently to CTLA-4, and inhibits interactions between CTLA-4 and its ligand by occluding the ligand-binding motif on CTLA-4 as shown crystallographically. We used H11 to visualize CTLA-4 expression in vivo using whole-animal immuno-PET, finding that surface-accessible CTLA-4 is largely confined to the tumor microenvironment. Despite this, H11-mediated CTLA-4 blockade has minimal effects on antitumor responses. Installation of the murine IgG2a constant region on H11 dramatically enhances its antitumor response. Coadministration of the monovalent H11 VHH blocks the efficacy of a full-sized therapeutic antibody. We were thus able to demonstrate that CTLA-4-binding antibodies require an Fc domain for antitumor effect.

Published
2018

45. Structural Insights into Thioether Bond Formation in the Biosynthesis of Sactipeptides

Author

Yumerefendi, H., Hwang, S., Kuhlman, B., Grove, T.L., Almo, S.C., Bowers, A.A., Himes, P.M., and Bonanno, J.B.

Abstract

Sactipeptides are ribosomally synthesized peptides that contain a characteristic thioether bridge (sactionine bond) that is installed posttranslationally and is absolutely required for their antibiotic activity. Sactipeptide biosynthesis requires a unique family of radical SAM enzymes, which contain multiple [4Fe-4S] clusters, to form the requisite thioether bridge between a cysteine and the α-carbon of an opposing amino acid through radical-based chemistry. Here we present the structure of the sactionine bond-forming enzyme CteB, from Clostridium thermocellum ATCC 27405, with both SAM and an N-terminal fragment of its peptidyl-substrate at 2.04 Å resolution. CteB has the (β/α)6-TIM barrel fold that is characteristic of radical SAM enzymes, as well as a C-terminal SPASM domain that contains two auxiliary [4Fe-4S] clusters. Importantly, one [4Fe-4S] cluster in the SPASM domain exhibits an open coordination site in absence of peptide substrate, which is coordinated by a peptidyl-cysteine residue in the bound state. The crystal structure of CteB also reveals an accessory N-terminal domain that has high structural similarity to a recently discovered motif present in several enzymes that act on ribosomally synthesized and post-translationally modified peptides (RiPPs), known as a RiPP precursor peptide recognition element (RRE). This crystal structure is the first of a sactionine bond forming enzyme and sheds light on structures and mechanisms of other members of this class such as AlbA or ThnB.

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results