2AYL

2.0 Angstrom Crystal Structure of Manganese Protoporphyrin IX-reconstituted Ovine Prostaglandin H2 Synthase-1 Complexed With Flurbiprofen

Summary for 2AYL

• Entry DOI: 10.2210/pdb2ayl/pdb
• Related: 1EQG 1EQH 1HT5 1HT8 1PRH 1Q4G
• Descriptor: Prostaglandin G/H synthase 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: cyclooxygenase, non-steroidal anti-inflammatory drug, peroxidase, prostaglandin synthase, egf-like domain, membrane binding domain, maganese protoporphyrin ix, oxidoreductase
• Biological source: Ovis aries (sheep)
• Total number of polymer chains: 2
• Total formula weight: 135842.83

Authors

Gupta, K.,Selinsky, B.S.,Loll, P.J. (deposition date: 2005-09-07, release date: 2006-01-24, Last modification date: 2024-11-20)

Primary citation

Gupta, K.,Selinsky, B.S.,Loll, P.J.
2.0 angstroms structure of prostaglandin H2 synthase-1 reconstituted with a manganese porphyrin cofactor.
Acta Crystallogr.,Sect.D, 62:151-156, 2006

PubMed Abstract: 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.

PubMed: 16421446
DOI: 10.1107/S0907444905036309

Experimental method

X-RAY DIFFRACTION (2 Å)