The crystal structure of chloroperoxidase: a heme peroxidase--cytochrome P450 functional hybrid.
BACKGROUND
Chloroperoxidase (CPO) is a versatile heme-containing enzyme that exhibits peroxidase, catalase and cytochrome P450-like activities in addition to catalyzing halogenation reactions. The structure determination of CPO was undertaken to help elucidate those structural features that enable the enzyme to exhibit these multiple activities.


RESULTS
Despite functional similarities with other heme enzymes, CPO folds into a novel tertiary structure dominated by eight helical segments. The catalytic base, required to cleave the peroxide O-O bond, is glutamic acid rather than histidine as in other peroxidases. CPO contains a hydrophobic patch above the heme that could be the binding site for substrates that undergo P450-like reactions. The crystal structure also shows extensive glycosylation with both N- and O-linked glycosyl chains.


CONCLUSIONS
The proximal side of the heme in CPO resembles cytochrome P450 because a cysteine residue serves as an axial heme ligand, whereas the distal side of the heme is 'peroxidase-like' in that polar residues form the peroxide-binding site. Access to the heme pocket is restricted to the distal face such that small organic substrates can interact with the iron-linked oxygen atom which accounts for the P450-like reactions catalyzed by chloroperoxidase.
Sundaramoorthy
M
M
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717, USA.
Terner
J
J
Poulos
T L
TL
D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D002711:Chloride Peroxidase / Q000737:chemistry*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry; D006031:Glycosylation; D006418:Heme / Q000737:chemistry; D006420:Hemeproteins / Q000737:chemistry / Q000145:classification; D006860:Hydrogen Bonding; D007501:Iron / Q000737:chemistry; D003904:Mitosporic Fungi / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D005656:Fungal Proteins; D006420:Hemeproteins; D018698:Glutamic Acid; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D007501:Iron; D002711:Chloride Peroxidase