1j4x
From Proteopedia
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HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE C124S MUTANT-PEPTIDE COMPLEX
Overview
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.
About this Structure
1J4X is a Single protein structure of sequence from Homo sapiens. This structure superseeds the now removed PDB entry 1F5D. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 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
Page seeded by OCA on Mon Nov 12 17:37:25 2007
