7s5s | pdb_00007s5s

CTX-M-15 WT in complex with BLIP WT

spinqualitylabelsall models 7s5s, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7s5s is a 2 chain structure with sequence from Escherichia coli and Streptomyces clavuligerus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C7S9T0_ECOLX Publication Abstract from PubMed beta-lactamases inactivate beta-lactam antibiotics leading to drug resistance. Consequently, inhibitors of beta-lactamases can combat this resistance, and the beta-lactamase inhibitory protein (BLIP) is a naturally occurring inhibitor. The widespread CTX-M-14 and CTX-M-15 beta-lactamases have an 83% sequence identity. In this study, we show that BLIP weakly inhibits CTX-M-14 but potently inhibits CTX-M-15. The structure of the BLIP/CTX-M-15 complex reveals that binding is associated with a conformational change of an active site loop of beta-lactamase. Surprisingly, the loop structure in the complex is similar to that in a drug-resistant variant (N106S) of CTX-M-14. We hypothesized that the pre-established favorable loop conformation of the N106S mutant would facilitate binding. The N106S substitution results in a ~100- and 10-fold increase in BLIP inhibition potency for CTX-M-14 and CTX-M-15, respectively. Thus, this indicates that an active site loop in beta-lactamase toggles between conformations that control antibiotic hydrolysis and inhibitor susceptibility. These findings highlight the role of accessible active site conformations in controlling enzyme activity and inhibitor susceptibility as well as the influence of mutations in selectively stabilizing discrete conformations. An active site loop toggles between conformations to control antibiotic hydrolysis and inhibition potency for CTX-M beta-lactamase drug-resistance enzymes.,Lu S, Hu L, Lin H, Judge A, Rivera P, Palaniappan M, Sankaran B, Wang J, Prasad BVV, Palzkill T Nat Commun. 2022 Nov 7;13(1):6726. doi: 10.1038/s41467-022-34564-3. PMID:36344533 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also TEM1-beta-Lactamase/beta-lactamase Inhibitor Protein (BLIP)

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