3B6D

Crystal Structure of Streptomyces Cholesterol Oxidase H447Q/E361Q mutant (1.2A)

Summary for 3B6D

• Entry DOI: 10.2210/pdb3b6d/pdb
• Related: 3B3R
• Descriptor: Cholesterol oxidase, SULFATE ION, FLAVIN-N7 PROTONATED-ADENINE DINUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: flavoenzyme, flavin, oxidoreductase, flavin activation, cholesterol oxidase, cholesterol metabolism, fad, flavoprotein, lipid metabolism, secreted, steroid metabolism
• Biological source: Streptomyces sp.
• Cellular location: Secreted: P12676
• Total number of polymer chains: 1
• Total formula weight: 55841.30

Authors

Lyubimov, A.Y.,Vrielink, A. (deposition date: 2007-10-29, release date: 2007-12-18, Last modification date: 2023-11-01)

Primary citation

Lyubimov, A.Y.,Heard, K.,Tang, H.,Sampson, N.S.,Vrielink, A.
Distortion of flavin geometry is linked to ligand binding in cholesterol oxidase
Protein Sci., 16:2647-2656, 2007

PubMed Abstract: Two high-resolution structures of a double mutant of bacterial cholesterol oxidase in the presence or absence of a ligand, glycerol, are presented, showing the trajectory of glycerol as it binds in a Michaelis complex-like position in the active site. A group of three aromatic residues forces the oxidized isoalloxazine moiety to bend along the N5-N10 axis as a response to the binding of glycerol in the active site. Movement of these aromatic residues is only observed in the glycerol-bound structure, indicating that some tuning of the FAD redox potential is caused by the formation of the Michaelis complex during regular catalysis. This structural study suggests a possible mechanism of substrate-assisted flavin activation, improves our understanding of the interplay between the enzyme, its flavin cofactor and its substrate, and is of use to the future design of effective cholesterol oxidase inhibitors.

PubMed: 18029419
DOI: 10.1110/ps.073168207

Experimental method

X-RAY DIFFRACTION (1.2 Å)