5wae

ADC-7 in complex with boronic acid transition state inhibitor CR167ADC-7 in complex with boronic acid transition state inhibitor CR167

Structural highlights 5wae is a 4 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 1.804Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6DRA1_ACIBA Publication Abstract from PubMed Acinetobacter baumannii is a multidrug resistant pathogen that infects more than 12,000 patients each year in the US. Much of the resistance to beta-lactam antibiotics in Acinetobacter spp. is a result of class C beta-lactamases known as Acinetobacter-derived cephalosporinases (ADCs). ADCs are unaffected by clinically used -lactam-based beta-lactamase inhibitors. In this study, five boronic acid transition state analog inhibitors (BATSIs) were evaluated for inhibition of the class C cephalosporinase ADC-7. Our goal was to explore the properties of BATSIs designed to probe the R1 binding site. Ki values ranged from low micromolar to sub-nanomolar, and circular dichroism (CD) demonstrated that each inhibitor stabilizes the beta-lactamase-inhibitor complexes. Additionally, X-ray crystal structures of ADC-7 in complex with five inhibitors were determined (resolutions from 1.80-2.09 A). In the ADC-7/CR192 complex, the BATSI with the lowest Ki (0.45 nM) and greatest DeltaTm (+9 degrees C), a trifluoromethyl substituent interacts with Arg340. Arg340 is unique to ADCs and may play an important role in the inhibition of ADC-7. The ADC-7/BATSI complexes determined in this study shed light into the unique recognition sites in ADC enzymes, and also offer insight into further structure-based optimization of these inhibitors. Structure-based analysis of boronic acids as inhibitors of Acinetobacter-derived cephalosporinase-7 (ADC-7), a unique class C beta-lactamase.,Bouza AA, Swanson HC, Smolen KA, VanDine AL, Taracila MA, Romagnoli C, Caselli E, Prati F, Bonomo RA, Powers RA, Wallar BJ ACS Infect Dis. 2017 Nov 16. doi: 10.1021/acsinfecdis.7b00152. PMID:29144724 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

spinqualitylabelsall models 5wae, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image