Why ser and not thr brokers catalysis in the trypsin fold

Pelc LA, Chen Z, Gohara DW, Vogt AD, Pozzi N, Di Cera E Biochemistry 2015 Feb;54(7):1457-64 PMID: 25664608 Abstract Although Thr is equally represented as Ser in the human genome and as a nucleophile is as good as Ser, it is never found in the active site of the large family of trypsin-like proteases that […]

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Structural dynamics as a contributor to error-prone replication by an RNA-dependent RNA polymerase

Moustafa IM, Korboukh VK, Arnold JJ, Smidansky ED, Marcotte LL, Gohara DW, Yang X, Sánchez-Farrán MA, Filman D, Maranas JK, Boehr DD, Hogle JM, Colina CM, Cameron CE J. Biol. Chem. 2014 Dec;289(52):36229-48 PMID: 25378410 Abstract RNA viruses encoding high- or low-fidelity RNA-dependent RNA polymerases (RdRp) are attenuated. The ability to predict residues of the […]

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Sequence selectivity of macrolide-induced translational attenuation

Davis AR, Gohara DW, Yap MN Proc. Natl. Acad. Sci. U.S.A. 2014 Oct;111(43):15379-84 PMID: 25313041 Abstract The prevailing “plug-in-the-bottle” model suggests that macrolide antibiotics inhibit translation by binding inside the ribosome tunnel and indiscriminately arresting the elongation of every nascent polypeptide after the synthesis of six to eight amino acids. To test this model, we […]

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Next generation sequencing-based parallel analysis of melting kinetics of 4096 variants of a bacterial promoter

Heyduk E, Heyduk T Biochemistry 2014 Jan;53(2):282-92 PMID: 24359527 Abstract Promoter melting by bacterial RNA polymerase is a key step in transcription initiation. We used a next generation sequencing (NGS) based approach to analyze in parallel promoter melting of all 4096 sequence variants of the 6 bp -10 promoter element. We used NGS read count […]

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Crystal structure of prothrombin reveals conformational flexibility and mechanism of activation

Pozzi N, Chen Z, Gohara DW, Niu W, Heyduk T, Di Cera E J. Biol. Chem. 2013 Aug;288(31):22734-44 PMID: 23775088 Abstract The zymogen prothrombin is composed of fragment 1 containing a Gla domain and kringle-1, fragment 2 containing kringle-2, and a protease domain containing A and B chains. The prothrombinase complex assembled on the surface […]

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Conformational selection in trypsin-like proteases

Pozzi N, Vogt AD, Gohara DW, Di Cera E Curr. Opin. Struct. Biol. 2012 Aug;22(4):421-31 PMID: 22664096 Abstract For over four decades, two competing mechanisms of ligand recognition–conformational selection and induced-fit–have dominated our interpretation of protein allostery. Defining the mechanism broadens our understanding of the system and impacts our ability to design effective drugs and […]

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