PDBsum entry 2ayl

Oxidoreductase

PDB id: 2ayl

Contents

Protein chains

553 a.a. *

Ligands

NAG-NAG ×2

NAG-NAG-MAN-MAN-MAN ×2

NAG-NAG-MAN-MAN ×2

BOG ×7

FLP ×2

MNH ×2

GOL ×5

Waters ×891

* Residue conservation analysis

PDB id:

2ayl

Name:

Oxidoreductase

Title:

2.0 angstrom crystal structure of manganese protoporphyrin ix- reconstituted ovine prostaglandin h2 synthase-1 complexed with flurbiprofen

Structure:

Prostaglandin g/h synthase 1. Chain: a, b. Synonym: cyclooxygenase-1, cox-1, prostaglandin-endoperoxide synthase 1, prostaglandin h2 synthase 1, pgh synthase 1, pghs-1, phs 1. Ec: 1.14.99.1

Source:

Ovis aries. Sheep. Organism_taxid: 9940. Organ: seminal vesicle

Biol. unit:

Dimer (from PQS)

Resolution:

2.00Å R-factor: 0.218 R-free: 0.237

Authors:

K.Gupta,B.S.Selinsky,P.J.Loll

Key ref:

K.Gupta et al. (2006). 2.0 angstroms structure of prostaglandin H2 synthase-1 reconstituted with a manganese porphyrin cofactor. Acta Crystallogr D Biol Crystallogr, 62, 151-156. PubMed id: 16421446 DOI: 10.1107/S0907444905036309

Date:

07-Sep-05 Release date: 24-Jan-06

Protein chains

P05979  (PGH1_SHEEP) -  Prostaglandin G/H synthase 1 from Ovis aries

Seq: 600 a.a.

Struc: 553 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.1.14.99.1 - prostaglandin-endoperoxide synthase.
• Reaction: (5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = prostaglandin H2 + A + H2O

(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 × O2 = prostaglandin H2 + + H2O (Bound ligand (Het Group name = MNH) matches with 51.11% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1107/S0907444905036309

Acta Crystallogr D Biol Crystallogr 62:151-156 (2006)

PubMed id: 16421446

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

K.Gupta, B.S.Selinsky, P.J.Loll.

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.

Selected figure(s)

Figure 3.
Figure 3 Stereoviews of the peroxidase and cyclooxygenase active sites. (a) Superposition of the peroxidase sites of the Fe-PGHS and Mn-PGHS structures. The iron structure is shown in red and the manganese structure in blue. The protein backbone is represented by the yellow ribbon. (b) The Mn-PGHS structure, showing the anomalous difference Fourier map contoured at 6 [89][sigma] . The perspective of the viewer is similar to that in (a), but in (b) the porphyrin has been rotated slightly upward about a horizontal axis relative to the orientation shown in (a). (c) Superposition of the NSAID-binding sites of the 2.0 Å Fe-PGHS and Mn-PGHS structures (Gupta et al., 2004[90] [Gupta, K., Selinsky, B. S., Kaub, C. J., Katz, A. K. & Loll, P. J. (2004). J. Mol. Biol. 335, 503-518.]-[91][bluearr.gif] and this work); the color scheme is the same as in (a). The ligand in the Fe-PGHS structure is [92][alpha] -methyl-4-biphenylacetic acid (desfluoro-flurbiprofen). The flurbiprofen in the Mn-PGHS structure occupies two alternate positions of roughly equal occupancy, corresponding to two alternate positions for the F atom. The two fluorine positions are marked by asterisks. Two alternate rotamers are observed for the side chain of Ser530 in both the Fe- and Mn-PGHS structures.

The above figure is reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2006, 62, 151-156) copyright 2006.

Figure was selected by the author.