1ga0 | pdb_00001ga0

STRUCTURE OF THE E. CLOACAE GC1 BETA-LACTAMASE WITH A CEPHALOSPORIN SULFONE INHIBITOR

spinqualitylabelsall models 1ga0, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1ga0 is a 1 chain structure with sequence from Enterobacter cloacae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.6Å Ligands: DVR, GOL, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q59401_ENTCL Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The crystallographic structure of the Enterobacter cloacae GC1 extended-spectrum class C beta-lactamase, inhibited by a new 7-alkylidenecephalosporin sulfone, has been determined by X-ray diffraction at 100 K to a resolution of 1.6 A. The crystal structure was solved by molecular replacement using the unliganded structure [Crichlow et al. (1999) Biochemistry 38, 10256-10261] and refined to a crystallographic R-factor equal to 0.183 (R(free) 0.208). Cryoquenching of the reaction of the sulfone with the enzyme produced an intermediate that is covalently bound via Ser64. After acylation of the beta-lactam ring, the dihydrothiazine dioxide ring opened with departure of the sulfinate. Nucleophilic attack of a side chain pyridine nitrogen atom on the C6 atom of the resultant imine yielded a bicyclic aromatic system which helps to stabilize the acyl enzyme to hydrolysis. A structural assist to this resonance stabilization is the positioning of the anionic sulfinate group between the probable catalytic base (Tyr150) and the acyl ester bond so as to block the approach of a potentially deacylating water molecule. Comparison of the liganded and unliganded protein structures showed that a major movement (up to 7 A) and refolding of part of the Omega-loop (215-224) accompanies the binding of the inhibitor. This conformational flexibility in the Omega-loop may form the basis of an extended-spectrum activity of class C beta-lactamases against modern cephalosporins. Inhibition of class C beta-lactamases: structure of a reaction intermediate with a cephem sulfone.,Crichlow GV, Nukaga M, Doppalapudi VR, Buynak JD, Knox JR Biochemistry. 2001 May 29;40(21):6233-9. PMID:11371184 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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