1J4X

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

Replaces:  1F5D

Summary for 1J4X

• Entry DOI: 10.2210/pdb1j4x/pdb
• Descriptor: DUAL SPECIFICITY PROTEIN PHOSPHATASE 3, DDE(AHP)(TPO)G(PTR)VATR (3 entities in total)
• Functional Keywords: hydrolase, protein dual-specificity phosphatase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P51452
• Total number of polymer chains: 2
• Total formula weight: 21768.29

Authors

Schumacher, M.A.,Todd, J.L.,Tanner, K.G.,Denu, J.M. (deposition date: 2001-12-13, release date: 2001-12-19, Last modification date: 2023-12-27)

Primary citation

Schumacher, M.A.,Todd, J.L.,Rice, A.E.,Tanner, K.G.,Denu, J.M.
Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein Phosphatase.
Biochemistry, 41:3009-3017, 2002

PubMed Abstract: 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.

PubMed: 11863439
DOI: 10.1021/bi015799l

Experimental method

X-RAY DIFFRACTION (2.75 Å)