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PDBsum entry 2ayl

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Oxidoreductase PDB id
2ayl
Jmol
Contents
Protein chains
553 a.a.
Ligands
BOG ×7
NAG-NAG ×2
NAG-NAG-MAN-MAN-
MAN
×2
NAG-NAG-MAN-MAN ×2
FLP ×2
MNH ×2
GOL ×5
Waters ×891

References listed in PDB file
Key reference
Title 2.0 angstroms structure of prostaglandin h2 synthase-1 reconstituted with a manganese porphyrin cofactor.
Authors K.Gupta, B.S.Selinsky, P.J.Loll.
Ref. Acta Crystallogr D Biol Crystallogr, 2006, 62, 151-156. [DOI no: 10.1107/S0907444905036309]
PubMed id 16421446
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.
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 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.
PROCHECK
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