PDBsum entry 1vhr

Hydrolase

PDB id: 1vhr

Contents

Protein chains

178 a.a. *

Ligands

EPE

SO4

Waters ×141

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Crystal structure of the dual specificity protein phosphatase vhr.
• Authors: J.Yuvaniyama, J.M.Denu, J.E.Dixon, M.A.Saper.
• Ref.: Science, 1996, 272, 1328-1331. [DOI no: 10.1126/science.272.5266.1328]
• PubMed id: 8650541

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a percentage match of 86%.

Abstract

Dual specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle. Here, the crystal structure of a human DSP, vaccinia H1-related phosphatase (or VHR), was determined at 2.1 angstrom resolution. A shallow active site pocket in VHR allows for the hydrolysis of phosphorylated serine, threonine, or tyrosine protein residues, whereas the deeper active site of protein tyrosine phosphatases (PTPs) restricts substrate specificity to only phosphotyrosine. Positively charged crevices near the active site may explain the enzyme's preference for substrates with two phosphorylated residues. The VHR structure defines a conserved structural scaffold for both DSPs and PTPs. A "recognition region," connecting helix alpha1 to strand beta1, may determine differences in substrate specificity between VHR, the PTPs, and other DSPs.

Secondary reference #1

• Title: The purification and characterization of a human dual-Specific protein tyrosine phosphatase.
• Authors: J.M.Denu, G.Zhou, L.Wu, R.Zhao, J.Yuvaniyama, M.A.Saper, J.E.Dixon.
• Ref.: J Biol Chem, 1995, 270, 3796-3803.
• PubMed id: 7876121

Secondary reference #2

• Title: The catalytic role of cys124 in the dual specificity phosphatase vhr.
• Authors: G.Zhou, J.M.Denu, L.Wu, J.E.Dixon.
• Ref.: J Biol Chem, 1994, 269, 28084-28090.
• PubMed id: 7961745

Secondary reference #3

• Title: Expression cloning of a human dual-Specificity phosphatase.
• Authors: T.Ishibashi, D.P.Bottaro, A.Chan, T.Miki, S.A.Aaronson.
• Ref.: Proc Natl Acad Sci U S A, 1992, 89, 12170-12174. [DOI no: 10.1073/pnas.89.24.12170]
• PubMed id: 1281549