Document Detail


Role of E166 in the imine to enamine tautomerization of the clinical beta-lactamase inhibitor sulbactam.
MedLine Citation:
PMID:  19791797     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mechanism-based inhibitors of class A beta-lactamases, such as sulbactam, undergo a complex series of chemical reactions in the enzyme active site. Formation of a trans-enamine acyl-enzyme via a hydrolysis-prone imine is responsible for transient inhibition of the enzyme. Although the imine to enamine tautomerization is crucial to inhibition of the enzyme, there are no experimental data to suggest how this chemical transformation is catalyzed in the active site. In this report, we show that E166 acts as a general base to promote the imine to enamine tautomerization.
Authors:
Matthew Kalp; John D Buynak; Paul R Carey
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemistry     Volume:  48     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-27     Completed Date:  2009-11-17     Revised Date:  2014-11-09    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10196-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amines / chemistry*,  metabolism
Catalytic Domain
Enzyme Inhibitors / chemistry*,  metabolism*
Imines / chemistry*,  metabolism
Models, Molecular
Spectrum Analysis, Raman
Structure-Activity Relationship
Sulbactam / chemistry*,  metabolism*
beta-Lactamases / antagonists & inhibitors*
Grant Support
ID/Acronym/Agency:
R01 GM54072/GM/NIGMS NIH HHS; R56 GM054072/GM/NIGMS NIH HHS; R56 GM054072-13/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Amines; 0/Enzyme Inhibitors; 0/Imines; EC 3.5.2.6/beta-Lactamases; S4TF6I2330/Sulbactam
Comments/Corrections

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


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