7s0v

The role of an Asp-Asp pair in the structure, function and inhibition of CTX-M Class A Beta-lactamaseThe role of an Asp-Asp pair in the structure, function and inhibition of CTX-M Class A Beta-lactamase

Structural highlights 7s0v is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9L5C7_ECOLX Publication Abstract from PubMed The Asp233-Asp246 pair is highly conserved in Class A beta-lactamases, which hydrolyze beta-lactam antibiotics. Here, we characterize its function using CTX-M-14 beta-lactamase. The D233N mutant displayed decreased activity that is substrate-dependent, with reductions in kcat /Km ranging from 20% for nitrocefin to 6-fold for cefotaxime. In comparison, the mutation reduced the binding of a known reversible inhibitor by 10-fold. The mutant structures showed movement of the 213-219 loop and the loss of the Thr216-Thr235 hydrogen bond, which was restored by inhibitor binding. Mutagenesis of Thr216 further highlighted its contribution to CTX-M activity. These results demonstrate the importance of the aspartate pair to CTX-M hydrolysis of substrates with bulky side chains, while suggesting increased protein flexibility as a means to evolve drug resistance. Mutation of the conserved Asp-Asp pair impairs the structure, function, and inhibition of CTX-M Class A beta-lactamase.,Kemp MT, Nichols DA, Zhang X, Defrees K, Na I, Renslo AR, Chen Y FEBS Lett. 2021 Oct 26. doi: 10.1002/1873-3468.14215. PMID:34704263 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

spinqualitylabelsall models 7s0v, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image