4ERC

Structure of VHZ bound to metavanadate

Summary for 4ERC

• Entry DOI: 10.2210/pdb4erc/pdb
• Related: 2img
• Descriptor: Dual specificity protein phosphatase 23, oxido(dioxo)vanadium (3 entities in total)
• Functional Keywords: alpha beta, phosphatase(hydrolase), hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytosol: Q9BVJ7
• Total number of polymer chains: 2
• Total formula weight: 33418.15

Authors

Vyacheslav, K.,Alvan, C.H.,Sean, J.J. (deposition date: 2012-04-19, release date: 2012-12-19, Last modification date: 2024-02-28)

Primary citation

Kuznetsov, V.I.,Hengge, A.C.,Johnson, S.J.
New Aspects of the Phosphatase VHZ Revealed by a High-Resolution Structure with Vanadate and Substrate Screening.
Biochemistry, 51:9869-9879, 2012

PubMed Abstract: The recently discovered 150-residue human VHZ (VH1-related protein, Z member) is one of the smallest protein tyrosine phosphatases (PTPs) known and contains only the minimal structural elements common to all PTPs. We report a substrate screening analysis and a crystal structure of the VHZ complex with vanadate at 1.1 Å resolution, with a detailed structural comparison with other members of the protein tyrosine phosphatase family, including classical tyrosine-specific protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DSPs). A screen with 360 phosphorylated peptides shows VHZ efficiently catalyzes the hydrolysis of phosphotyrosine (pY)-containing peptides but exhibits no activity toward phosphoserine (pS) or phosphothreonine (pT) peptides. The new structure reveals a deep and narrow active site more typical of the classical tyrosine-specific PTPs. Despite the high degrees of structural and sequence similarity between VHZ and classical PTPs, its general acid IPD-loop is most likely conformationally rigid, in contrast to the flexible WPD counterpart of classical PTPs. VHZ also lacks substrate recognition domains and other domains typically found on classical PTPs. It is therefore proposed that VHZ is more properly classified as an atypical PTP rather than an atypical DSP, as has been suggested.

PubMed: 23145819
DOI: 10.1021/bi300908y

Experimental method

X-RAY DIFFRACTION (1.15 Å)