Structural highlights
Evolutionary Conservation
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Publication Abstract from PubMed
The intrinsic resistance of Mycobacterium tuberculosis to the beta-lactam class of antibiotics arises from a chromosomally encoded, extended spectrum, class A beta-lactamase, BlaC. Herein, we report the X-ray crystallographic structure of BlaC inhibited with clavulanate at a resolution of 1.7 A with an R-factor value of 0.180 and R-free value of 0.212 for the m/ z +154 clavulanate-derived fragment observed in the active site. Structural evidence reveals the presence of hydrogen bonds to the C1 carbonyl along with a coplanar arrangement of C1, C2, C3, and N4, which favors enolization to generate a trans-alpha,beta-eneamine, stabilizing the +154 adduct from hydrolysis. The irreversible inhibition of BlaC suggests that treatment of M. tuberculosis with a combination of a beta-lactam antibiotic and clavulanate may lead to rapid bactericidal activity.
Structure of the covalent adduct formed between Mycobacterium tuberculosis beta-lactamase and clavulanate.,Tremblay LW, Hugonnet JE, Blanchard JS Biochemistry. 2008 May 13;47(19):5312-6. Epub 2008 Apr 19. PMID:18422342[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tremblay LW, Hugonnet JE, Blanchard JS. Structure of the covalent adduct formed between Mycobacterium tuberculosis beta-lactamase and clavulanate. Biochemistry. 2008 May 13;47(19):5312-6. Epub 2008 Apr 19. PMID:18422342 doi:10.1021/bi8001055
