1hjf

Alteration of the co-substrate selectivity of deacetoxycephalosporin C synthase: The role of arginine-258

spinqualitylabelsall models 1hjf, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1hjf is a 1 chain structure with sequence from Streptomyces clavuligerus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.6Å Ligands: COI, FE2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CEFE_STRCL Catalyzes the step from penicillin N to deacetoxy-cephalosporin C. 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 Deacetoxycephalosporin C synthase is an iron(II) 2-oxoglutaratedependent oxygenase that catalyzes the oxidative ring-expansion of penicillin N to deacetoxycephalosporin C. The wild-type enzyme is only able to efficiently utilize 2-oxoglutarate and 2-oxoadipate as a 2-oxoacid co-substrate. Mutation of arginine 258, the side chain of which forms an electrostatic interaction with the 5-carboxylate of the 2-oxoglutarate co-substrate, to a glutamine residue reduced activity to about 5% of the wild-type enzyme with 2-oxoglutarate. However, other aliphatic 2-oxoacids, which were not co-substrates for the wild-type enzyme, were utilized by the R258Q mutant. These 2-oxoacids "rescued" catalytic activity to the level observed for the wild-type enzyme as judged by penicillin N and G conversion. These co-substrates underwent oxidative decarboxylation as observed for 2-oxoglutarate in the normal reaction with the wild-type enzyme. Crystal structures of the iron(II)- 2-oxo-3-methylbutanoate (1.5 A), and iron(II)-2-oxo-4-methylpentanoate (1.6 A) enzyme complexes were obtained, which reveal the molecular basis for this "chemical co-substrate rescue" and help to rationalize the co-substrate selectivity of 2-oxoglutaratedependent oxygenases. Alteration of the co-substrate selectivity of deacetoxycephalosporin C synthase. The role of arginine 258.,Lee HJ, Lloyd MD, Clifton IJ, Harlos K, Dubus A, Baldwin JE, Frere JM, Schofield CJ J Biol Chem. 2001 May 25;276(21):18290-5. Epub 2001 Feb 21. PMID:11279000 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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