1oev

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{{STRUCTURE_1oev| PDB=1oev | SCENE= }}
{{STRUCTURE_1oev| PDB=1oev | SCENE= }}
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'''OXIDATION STATE OF PROTEIN TYROSINE PHOSPHATASE 1B'''
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===OXIDATION STATE OF PROTEIN TYROSINE PHOSPHATASE 1B===
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==Overview==
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Protein tyrosine phosphatases regulate signal transduction pathways involving tyrosine phosphorylation and have been implicated in the development of cancer, diabetes, rheumatoid arthritis and hypertension. Increasing evidence suggests that the cellular redox state is involved in regulating tyrosine phosphatase activity through the reversible oxidization of the catalytic cysteine to sulphenic acid (Cys-SOH). But how further oxidation to the irreversible sulphinic (Cys-SO2H) and sulphonic (Cys-SO3H) forms is prevented remains unclear. Here we report the crystal structures of the regulatory sulphenic and irreversible sulphinic and sulphonic acids of protein tyrosine phosphatase 1B (PTP1B), an important enzyme in the negative regulation of the insulin receptor and a therapeutic target in type II diabetes and obesity. We also identify a sulphenyl-amide species that is formed through oxidation of its catalytic cysteine. Formation of the sulphenyl-amide causes large changes in the PTP1B active site, which are reversible by reduction with the cellular reducing agent glutathione. The sulphenyl-amide is a protective intermediate in the oxidative inhibition of PTP1B. In addition, it may facilitate reactivation of PTP1B by biological thiols and signal a unique state of the protein.
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The line below this paragraph, {{ABSTRACT_PUBMED_12802339}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 12802339 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12802339}}
==About this Structure==
==About this Structure==
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[[Category: Oxidative regulation]]
[[Category: Oxidative regulation]]
[[Category: Protein tyrosine phosphatase]]
[[Category: Protein tyrosine phosphatase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:45:27 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:31:25 2008''

Revision as of 05:31, 29 July 2008

Image:1oev.png

Template:STRUCTURE 1oev

OXIDATION STATE OF PROTEIN TYROSINE PHOSPHATASE 1B

Template:ABSTRACT PUBMED 12802339

About this Structure

1OEV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B., van Montfort RL, Congreve M, Tisi D, Carr R, Jhoti H, Nature. 2003 Jun 12;423(6941):773-7. PMID:12802339

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