Structural highlights
Function
BLAC_MYCTU
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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