Document Detail


Transpeptidase-mediated incorporation of D-amino acids into bacterial peptidoglycan.
MedLine Citation:
PMID:  21682301     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The β-lactams are the most important class of antibiotics in clinical use. Their lethal targets are the transpeptidase domains of penicillin binding proteins (PBPs), which catalyze the cross-linking of bacterial peptidoglycan (PG) during cell wall synthesis. The transpeptidation reaction occurs in two steps, the first being formation of a covalent enzyme intermediate and the second involving attack of an amine on this intermediate. Here we use defined PG substrates to dissect the individual steps catalyzed by a purified E. coli transpeptidase. We demonstrate that this transpeptidase accepts a set of structurally diverse D-amino acid substrates and incorporates them into PG fragments. These results provide new information on donor and acceptor requirements as well as a mechanistic basis for previous observations that noncanonical D-amino acids can be introduced into the bacterial cell wall.
Authors:
Tania J Lupoli; Hirokazu Tsukamoto; Emma H Doud; Tsung-Shing Andrew Wang; Suzanne Walker; Daniel Kahne
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-06-27
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  133     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-13     Completed Date:  2011-11-03     Revised Date:  2012-04-27    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10748-51     Citation Subset:  IM    
Affiliation:
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Amino Acids / chemistry*,  metabolism*
Escherichia coli / enzymology,  metabolism*
Peptidoglycan / metabolism*
Peptidyl Transferases / chemistry,  metabolism*
Stereoisomerism
Grant Support
ID/Acronym/Agency:
R01 GM066174/GM/NIGMS NIH HHS; R01 GM066174/GM/NIGMS NIH HHS; R01 GM066174-10/GM/NIGMS NIH HHS; R01 GM066174-11/GM/NIGMS NIH HHS; R01 GM076710/GM/NIGMS NIH HHS; R01 GM076710-04/GM/NIGMS NIH HHS; R01 GM076710-06/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Peptidoglycan; EC 2.3.2.12/Peptidyl Transferases

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


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