4olg

Crystal structure of AmpC beta-lactamase in complex with covalently bound N-formyl 7-aminocephalosporanic acidCrystal structure of AmpC beta-lactamase in complex with covalently bound N-formyl 7-aminocephalosporanic acid

Structural highlights 4olg 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 1.71Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AMPC_ECOLI This protein is a serine beta-lactamase with a substrate specificity for cephalosporins. Publication Abstract from PubMed Predicting substrates for enzymes of unknown function is a major postgenomic challenge. Substrate discovery, like inhibitor discovery, is constrained by our ability to explore chemotypes; it would be expanded by orders of magnitude if reactive sites could be probed with fragments rather than fully elaborated substrates, as is done for inhibitor discovery. To explore the feasibility of this approach, substrates of six enzymes from three different superfamilies were deconstructed into 41 overlapping fragments that were tested for activity or binding. Surprisingly, even those fragments containing the key reactive group had little activity, and most fragments did not bind measurably, until they captured most of the substrate features. Removing a single atom from a recognized substrate could often reduce catalytic recognition by 6 log-orders. To explore recognition at atomic resolution, the structures of three fragment complexes of the beta-lactamase substrate cephalothin were determined by X-ray crystallography. Substrate discovery may be difficult to reduce to the fragment level, with implications for function discovery and for the tolerance of enzymes to metabolite promiscuity. Pragmatically, this study supports the development of libraries of fully elaborated metabolites as probes for enzyme function, which currently do not exist. Substrate deconstruction and the nonadditivity of enzyme recognition.,Barelier S, Cummings JA, Rauwerdink AM, Hitchcock DS, Farelli JD, Almo SC, Raushel FM, Allen KN, Shoichet BK J Am Chem Soc. 2014 May 21;136(20):7374-82. doi: 10.1021/ja501354q. Epub 2014 May, 12. PMID:24791931 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

spinqualitylabelsall models 4olg, resolution 1.71Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image