2obi

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{{STRUCTURE_2obi| PDB=2obi | SCENE= }}
{{STRUCTURE_2obi| PDB=2obi | SCENE= }}
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'''Crystal structure of the Selenocysteine to Cysteine Mutant of human phospholipid hydroperoxide glutathione peroxidase (GPx4)'''
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===Crystal structure of the Selenocysteine to Cysteine Mutant of human phospholipid hydroperoxide glutathione peroxidase (GPx4)===
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==Overview==
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Phospholipid hydroperoxide glutathione peroxidase (GPx4) is a moonlighting selenoprotein, which has been implicated in anti-oxidative defense, sperm development, and cerebral embryogenesis. Among GPx-isoforms, GPx4 is unique because of its capability to reduce complex lipid hydroperoxides and its tendency toward polymerization, but the structural basis for these properties remained unclear. To address this, we solved the crystal structure of the catalytically active U46C mutant of human GPx4 to 1.55 A resolution. X-ray data indicated a monomeric protein consisting of four alpha-helices and seven beta-strands. GPx4 lacks a surface exposed loop domain, which appears to limit the accessibility of the active site of other GPx-isoforms, and these data may explain the broad substrate specificity of GPx4. The catalytic triad (C46, Q81, and W136) is localized at a flat impression of the protein surface extending into a surface exposed patch of basic amino acids (K48, K135, and R152) that also contains polar T139. Multiple mutations of the catalytic triad indicated its functional importance. Like the wild-type enzyme, the U46C mutant exhibits a strong tendency toward protein polymerization, which was prevented by reductants. Site-directed mutagenesis suggested involvement of the catalytic C46 and surface exposed C10 and C66 in polymer formation. In GPx4 crystals, these residues contact adjacent protein monomers.
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(as it appears on PubMed at http://www.pubmed.gov), where 17630701 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17630701}}
==About this Structure==
==About this Structure==
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[[Category: Selenoprotein]]
[[Category: Selenoprotein]]
[[Category: Thioredoxin-fold]]
[[Category: Thioredoxin-fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:33:33 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 11:50:47 2008''

Revision as of 08:51, 29 July 2008

Image:2obi.png

Template:STRUCTURE 2obi

Crystal structure of the Selenocysteine to Cysteine Mutant of human phospholipid hydroperoxide glutathione peroxidase (GPx4)

Template:ABSTRACT PUBMED 17630701

About this Structure

2OBI is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis for catalytic activity and enzyme polymerization of phospholipid hydroperoxide glutathione peroxidase-4 (GPx4)., Scheerer P, Borchert A, Krauss N, Wessner H, Gerth C, Hohne W, Kuhn H, Biochemistry. 2007 Aug 7;46(31):9041-9. Epub 2007 Jul 13. PMID:17630701

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