7cin

Crystal structure of the extended-spectrum class C beta-lactamase AmpC BER with the ordered R2 loopCrystal structure of the extended-spectrum class C beta-lactamase AmpC BER with the ordered R2 loop

Structural highlights 7cin is a 2 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7900636Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A7TUE6_ECOLX Publication Abstract from PubMed AmpC BER is an extended-spectrum (ES) class C beta-lactamase with a two-amino-acid insertion in the H10 helix region located at the boundary of the active site compared with its narrow spectrum progenitor. The crystal structure of the wild-type AmpC BER revealed that the insertion widens the active site by restructuring the flexible H10 helix region, which is the structural basis for its ES activity. Besides, two sulfates originated from the crystallization solution were observed in the active site. The presence of sulfate-binding subsites, together with the recognition of ring-structured chemical scaffolds by AmpC BER, led us to perform in silico molecular docking experiments with halisulfates, natural products isolated from marine sponge. Inspired by the snug fit of halisulfates within the active site, we demonstrated that halisulfate 3 and 5 significantly inhibit ES class C beta-lactamases. Especially, halisulfate 5 is comparable to avibactam in terms of inhibition efficiency; it inhibits the nitrocefin-hydrolyzing activity of AmpC BER with a Ki value of 5.87 muM in a competitive manner. Furthermore, halisulfate 5 displayed moderate and weak inhibition activities against class A and class B/D enzymes, respectively. The treatment of beta-lactamase inhibitors (BLIs) in combination with beta-lactam antibiotics is a working strategy to cope with infections by pathogens producing ES beta-lactamases. Considering the emergence and dissemination of enzymes insensitive to clinically-used BLIs, the broad inhibition spectrum and structural difference of halisulfates would be used to develop novel BLIs that can escape the bacterial resistance mechanism mediated by beta-lactamases. Crystal structure of AmpC BER and molecular docking lead to the discovery of broad inhibition activities of halisulfates against beta-lactamases.,Jeong BG, Na JH, Bae DW, Park SB, Lee HS, Cha SS Comput Struct Biotechnol J. 2020 Dec 17;19:145-152. doi:, 10.1016/j.csbj.2020.12.015. eCollection 2021. PMID:33425247 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

spinqualitylabelsall models 7cin, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image