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PDBsum entry 2ayl
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Oxidoreductase
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PDB id
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2ayl
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References listed in PDB file
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Key reference
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Title
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2.0 angstroms structure of prostaglandin h2 synthase-1 reconstituted with a manganese porphyrin cofactor.
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Authors
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K.Gupta,
B.S.Selinsky,
P.J.Loll.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2006,
62,
151-156.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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The above figure is
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2006,
62,
151-156)
copyright 2006.
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