Document Detail


Structure of a Clostridium botulinum C143S thiaminase I/thiamin complex reveals active site architecture .
MedLine Citation:
PMID:  24079939     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Thiaminases are responsible for the degradation of thiamin and its metabolites. Two classes of thiaminases have been identified based on their three-dimensional structures and their requirements for a nucleophilic second substrate. Although the reactions of several thiaminases have been characterized, the physiological role of thiamin degradation is not fully understood. We have determined the three-dimensional X-ray structure of an inactive C143S mutant of Clostridium botulinum (Cb) thiaminase I with bound thiamin at 2.2 Å resolution. The C143S/thiamin complex provides atomic level details of the orientation of thiamin upon binding to Cb-thiaminase I and the identity of active site residues involved in substrate binding and catalysis. The specific roles of active site residues were probed by using site directed mutagenesis and kinetic analyses, leading to a detailed mechanism for Cb-thiaminase I. The structure of Cb-thiaminase I is also compared to the functionally similar but structurally distinct thiaminase II.
Authors:
Megan D Sikowitz; Brateen Shome; Yang Zhang; Tadhg P Begley; Steven E Ealick
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-10-25
Journal Detail:
Title:  Biochemistry     Volume:  52     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-05     Completed Date:  2014-01-17     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7830-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Alkyl and Aryl Transferases / chemistry*,  genetics*,  metabolism
Bacterial Proteins / chemistry*,  genetics*,  metabolism
Catalytic Domain
Clostridium botulinum / chemistry,  enzymology*,  genetics
Crystallography, X-Ray
Kinetics
Models, Molecular
Mutation, Missense*
Protein Structure, Secondary
Thiamine / chemistry,  metabolism*
Grant Support
ID/Acronym/Agency:
DK44083/DK/NIDDK NIH HHS; DK67081/DK/NIDDK NIH HHS; GM103403/GM/NIGMS NIH HHS; P41 GM103403/GM/NIGMS NIH HHS; R01 DK044083/DK/NIDDK NIH HHS; R01 DK067081/DK/NIDDK NIH HHS; R37 DK044083/DK/NIDDK NIH HHS; T32 GM008500/GM/NIGMS NIH HHS; T32GM008500/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Bacterial Proteins; EC 2.5.-/Alkyl and Aryl Transferases; EC 2.5.1.2/thiamin pyridinylase; X66NSO3N35/Thiamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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