2jc7

The crystal structure of the carbapenemase OXA-24 reveals new insights into the mechanism of carbapenem-hydrolysis

spinqualitylabelsall models 2jc7, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2jc7 is a 1 chain structure with sequence from Acinetobacter baumannii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8RLA6_ACIBA 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 Combating bacterial resistance to beta-lactams, the most widely used antibiotics, is an emergent and clinically important challenge. OXA-24 is a class D beta-lactamase isolated from a multiresistant epidemic clinical strain of Acinetobacter baumannii. We have investigated how OXA-24 specifically hydrolyzes the last resort carbapenem antibiotic, and we have determined the crystal structure of OXA-24 at a resolution of 2.5 A. The structure shows that the carbapenem's substrate specificity is determined by a hydrophobic barrier that is established through the specific arrangement of the Tyr-112 and Met-223 side chains, which define a tunnel-like entrance to the active site. The importance of these residues was further confirmed by mutagenesis studies. Biochemical and microbiological analyses of specific point mutants selected on the basis of structural criteria significantly reduced the catalytic efficiency (k(cat)/K(m)) against carbapenems, whereas the specificity for oxacillin was noticeably increased. This is the previously unrecognized crystal structure that has been obtained for a class D carbapenemase enzyme. Accordingly, this information may help to improve the development of effective new drugs to combat beta-lactam resistance. More specifically, it may help to overcome carbapenem resistance in A. baumannii, probably one of the most worrying infectious threats in hospitals worldwide. Crystal structure of the carbapenemase OXA-24 reveals insights into the mechanism of carbapenem hydrolysis.,Santillana E, Beceiro A, Bou G, Romero A Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5354-9. Epub 2007 Mar 20. PMID:17374723 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA