1J4X

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

「1F5D」から置き換えられました

1J4X の概要

• エントリーDOI: 10.2210/pdb1j4x/pdb
• 分子名称: DUAL SPECIFICITY PROTEIN PHOSPHATASE 3, DDE(AHP)(TPO)G(PTR)VATR (3 entities in total)
• 機能のキーワード: hydrolase, protein dual-specificity phosphatase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P51452
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 21768.29

構造登録者

Schumacher, M.A.,Todd, J.L.,Tanner, K.G.,Denu, J.M. (登録日: 2001-12-13, 公開日: 2001-12-19, 最終更新日: 2023-12-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.75 Å)