3cox
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CRYSTAL STRUCTURE OF CHOLESTEROL OXIDASE COMPLEXED WITH A STEROID SUBSTRATE. IMPLICATIONS FOR FAD DEPENDENT ALCOHOL OXIDASES
OverviewOverview
Cholesterol oxidase from Brevibacterium sterolicum is a flavin-dependent, enzyme that catalyzes the oxidation and isomerization of 3 beta-hydroxy, steroids with a double bond at delta 5-delta 6 of the steroid ring, backbone. The crystal structure of the free enzyme in the absence of a, steroid substrate has previously been determined. In this paper we report, the crystal structure of the complex of cholesterol oxidase with the, steroid substrate dehydroisoandrosterone, refined at 1.8-A resolution. The, final crystallographic R-value is 15.7% for all reflections between 10.0-, and 1.8-A resolution. The steroid is buried within the protein in an, internal cavity which, in the free enzyme crystal structure, was occupied, by a lattice of water molecules. The conformations of a number of side, chains lining the active-site cavity have changed in order to accommodate, the steroid substrate. A loop region of the structure between residues 70, and 90 differs significantly between the substrate-free and, substrate-bound forms of the enzyme, presumably to facilitate binding of, the steroid. The hydroxyl group of the steroid substrate is, hydrogen-bonded to both the flavin ring system of the FAD cofactor and a, bound water molecule. FAD-dependent cholesterol oxidase shares significant, structural homology with another flavoenzyme, glucose oxidase, suggesting, that it might also be a member of the glucose-methanol-choline (GMC), oxidoreductase family. Although there is only limited sequence homology, a, superposition of these two structures reveals a conserved histidine, residue within hydrogen-bonding distance of the active-site water, molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
About this StructureAbout this Structure
3COX is a Single protein structure of sequence from Brevibacterium sterolicum with FAD as ligand. This structure superseeds the now removed PDB entry 1COX. Active as Cholesterol oxidase, with EC number 1.1.3.6 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of cholesterol oxidase complexed with a steroid substrate: implications for flavin adenine dinucleotide dependent alcohol oxidases., Li J, Vrielink A, Brick P, Blow DM, Biochemistry. 1993 Nov 2;32(43):11507-15. PMID:8218217
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