Logo image
2.0 angstroms structure of prostaglandin H2 synthase-1 reconstituted with a manganese porphyrin cofactor
Journal article

2.0 angstroms structure of prostaglandin H2 synthase-1 reconstituted with a manganese porphyrin cofactor

Kushol Gupta, Barry S Selinsky and Patrick J Loll
Acta crystallographica. Section D, Biological crystallography, v 62(Pt 2), pp 151-156
Feb 2006
PMID: 16421446

Abstract

Animals Heme - metabolism Manganese - metabolism Prostaglandin-Endoperoxide Synthases - chemistry Prostaglandin-Endoperoxide Synthases - metabolism Protoporphyrins - metabolism Sheep Catalysis Porphyrins - metabolism Protoporphyrins - chemistry Iron - metabolism Peroxidase - chemistry
Prostaglandin H2 synthase (EC 1.14.99.1) is a clinically important drug target that catalyzes two key steps in the biosynthesis of the eicosanoid hormones. The enzyme contains spatially distinct cyclooxygenase and peroxidase active sites, both of which require a heme cofactor. Substitution of ferric heme by Mn(III) protoporphyrin IX greatly diminishes the peroxidase activity, but has little effect on the cyclooxygenase activity. Here, the 2.0 angstroms resolution crystal structure of the Mn(III) form of ovine prostaglandin H2 synthase-1 is described (R = 21.8%, R(free) = 23.7%). Substitution of Mn(III) for Fe(III) causes no structural perturbations in the protein. However, the out-of-plane displacement of the manganese ion with respect to the porphyrin is greater than that of the iron by approximately 0.2 angstroms. This perturbation may help to explain the altered catalytic properties of the manganese enzyme.

Metrics

12 Record Views
26 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
Web of Science research areas
Biochemical Research Methods
Biochemistry & Molecular Biology
Biophysics
Crystallography
Logo image