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1j4x

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{{STRUCTURE_1j4x| PDB=1j4x | SCENE= }}
{{STRUCTURE_1j4x| PDB=1j4x | SCENE= }}
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'''HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE C124S MUTANT-PEPTIDE COMPLEX'''
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===HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE C124S MUTANT-PEPTIDE COMPLEX===
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==Overview==
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Human VHR (vaccinia H1 related phosphatase) is a member of the dual-specificity phosphatases (DSPs) that often act on bisphosphorylated protein substrates. Unlike most DSPs, VHR displays a strong preference for dephosphorylating phosphotyrosine residues over phosphothreonine residues. Here we describe the 2.75 A crystal structure of the C124S inactive VHR mutant in complex with a bisphosphorylated peptide corresponding to the MAP kinase activation lip. This structure and subsequent biochemical studies revealed the basis for the strong preference for hydrolyzing phosphotyrosine within bisphosphorylated substrates containing -pTXpY-. In the structure, the two phospho residues are oriented into distinct pockets; the phosphotyrosine is bound in the exposed yet deep active site cleft while the phosphothreonine is loosely tethered into a nearby basic pocket containing Arg(158). As this structure is the first substrate-enzyme complex reported for the DSP family of enzymes, these results provide the first glimpse into how DSPs bind their protein substrates.
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(as it appears on PubMed at http://www.pubmed.gov), where 11863439 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11863439}}
==About this Structure==
==About this Structure==
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[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Protein dual-specificity phosphatase]]
[[Category: Protein dual-specificity phosphatase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:48:34 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 14:30:29 2008''

Revision as of 11:30, 1 July 2008

Image:1j4x.png

Template:STRUCTURE 1j4x

HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE C124S MUTANT-PEPTIDE COMPLEX

Template:ABSTRACT PUBMED 11863439

About this Structure

1J4X is a Single protein structure of sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1f5d. Full crystallographic information is available from OCA.

Reference

Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein Phosphatase., Schumacher MA, Todd JL, Rice AE, Tanner KG, Denu JM, Biochemistry. 2002 Mar 5;41(9):3009-17. PMID:11863439

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