PGHS-1 Peroxidase
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Structural comparisons between
fungal peroxidases and mammalian peroxidases suggest that they arose from a
common percursor. Here, the structures of lignin peroxidase (LiP), cytochrome
c peroxidase (CCP), myeloperoxidase (MPO), and PGHS peroxidase share the same
features such as catalytic site helices (green), the scaffolding helices
(light blue) around the heme (red) and functional (arrows) or vestigial (*)
calcium binding sites. |
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Accessible surface area views of
the fungal peroxidases and mammalian peroxidases show how buried the heme
(red) is in many peroxidases except PGHS, which uses larger hydrophobic
hydroperoxides (e.g., PGG2, 15-HPETE, etc.) as substrates rather than hydrogen
peroxide. The structures shown are lignin peroxidase (LiP), cytochrome c
peroxidase (CCP), myeloperoxidase (MPO), and PGHS peroxidase. References of Interest Picot, D., Loll, P. J., and Garavito, R. M. (1994) "The X-ray
crystal structure of the membrane protein prostaglandin H2
synthase-1." Nature (London) 367, 243-249. Garavito R. M., Picot, D., and Loll, P. J. (1994) Prostaglandin H
synthase. Curr. Opinion Struct. Biol. 4, 529-535. Malkowski, M.G., Theisen, M. J., Scharmen, A., and Garavito, R. M. (2000)
"The formation of stable fatty acid substrate complexes in prostaglandin
H synthase-1." Archives Biochem. Biophys. 380, 39-45. Seibold, S.A., Cerda, J.F., Mulichak, A. M., Song, I., Garavito, R. M.,
Arakawa, T., Smith, W.L., and Babcock, G.T. (2000). "Peroxidase activity
in prostaglandin endoperoxide H synthase-1 occurs with a neutral histidine
proximal heme ligand." Biochemistry 39, 6616-6624. Schelvis, J. P. M., Seibold, S.A., Cerda, J.F., Garavito, R. M., Arakawa,
T., and Babcock, G.T. (2000). "Interaction of nitric oxide with
prostaglandin endoperoxide H synthase: Implications for Fe-His bond cleavage
in heme proteins." J. Phys. Chem. B 104, 10844-10850. Malkowski, M. G., DeWitt, D. L., Garavito, R. M. (2002) "The
Structures of Prostaglandin Endoperoxide H Synthases-1 and -2".
Prostaglandins and other Lipid Mediators 68-69, 129-52. Garavito, R. M. and Mulichak, A. M. (2003) The structure of mammalian cyclooxygenases. Annu. Rev. Biophys. Biomolec. Struct. 32, 183-206.
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