1hjf | pdb_00001hjf

File:1hjf.gif

spinqualitylabelsall models 1hjf, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

ALTERATION OF THE CO-SUBSTRATE SELECTIVITY OF DEACETOXYCEPHALOSPORIN C SYNTHASE: THE ROLE OF ARGININE-258

Overview

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.

About this Structure

1HJF is a Single protein structure of sequence from Streptomyces clavuligerus with FE2 and COI as ligands. Structure known Active Sites: COI and FE. Full crystallographic information is available from OCA.

Reference

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

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