PDBsum entry 1j4x

Hydrolase

PDB id: 1j4x

Contents

Protein chains

178 a.a. *

11 a.a. *

Waters ×66

* Residue conservation analysis

PDB id:

1j4x

Name:

Hydrolase

Title:

Human vh1-related dual-specificity phosphatase c124s mutant-peptide complex

Structure:

Dual specificity protein phosphatase 3. Chain: a. Engineered: yes. Mutation: yes. Dde(ahp)(tpo)g(ptr)vatr. Chain: d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes

Biol. unit:

Dimer (from PQS)

Resolution:

2.75Å R-factor: 0.192 R-free: 0.260

Authors:

M.A.Schumacher,J.L.Todd,K.G.Tanner,J.M.Denu

Key ref:

M.A.Schumacher et al. (2002). Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein Phosphatase. Biochemistry, 41, 3009-3017. PubMed id: 11863439 DOI: 10.1021/bi015799l

Date:

13-Dec-01 Release date: 19-Dec-01

Supersedes:

1f5d

Protein chain

P51452  (DUS3_HUMAN) -  Dual specificity protein phosphatase 3 from Homo sapiens

Seq: 185 a.a.

Struc: 178 a.a.*

Protein chain

No UniProt id for this chain

Struc: 11 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 2: Chain A: E.C.3.1.3.16 - protein-serine/threonine phosphatase.
• Reaction:
  1. O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate
  2. O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate
• Enzyme class 3: Chain A: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/bi015799l

Biochemistry 41:3009-3017 (2002)

PubMed id: 11863439

Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein Phosphatase.

M.A.Schumacher, J.L.Todd, A.E.Rice, K.G.Tanner, J.M.Denu.

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.