PDBsum entry 1r6h

Hydrolase

PDB id: 1r6h

Contents

Protein chain

172 a.a. *

* Residue conservation analysis

PDB id:

1r6h

Name:

Hydrolase

Title:

Solution structure of human prl-3

Structure:

Protein tyrosine phosphatase type iva, member 3 isoform 1. Chain: a. Synonym: prl-3 phosphatase. Engineered: yes

Source:

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

NMR struc:

20 models

Authors:

G.Kozlov,K.Gehring,I.Ekiel

Key ref:

G.Kozlov et al. (2004). Structural insights into molecular function of the metastasis-associated phosphatase PRL-3. J Biol Chem, 279, 11882-11889. PubMed id: 14704153 DOI: 10.1074/jbc.M312905200

Date:

15-Oct-03 Release date: 13-Jan-04

Protein chain

O75365  (TP4A3_HUMAN) -  Protein tyrosine phosphatase type IVA 3 from Homo sapiens

Seq: 173 a.a.

Struc: 172 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

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

Key reference

DOI no: 10.1074/jbc.M312905200

J Biol Chem 279:11882-11889 (2004)

PubMed id: 14704153

Structural insights into molecular function of the metastasis-associated phosphatase PRL-3.

G.Kozlov, J.Cheng, E.Ziomek, D.Banville, K.Gehring, I.Ekiel.

ABSTRACT

Phosphatases and kinases are the cellular signal transduction enzymes that control protein phosphorylation. PRL phosphatases constitute a novel class of small (20 kDa), prenylated phosphatases with oncogenic activity. In particular, PRL-3 is consistently overexpressed in liver metastasis in colorectal cancer cells and represents a new therapeutic target. Here, we present the solution structure of PRL-3, the first structure of a PRL phosphatase. The structure places PRL phosphatases in the class of dual specificity phosphatases with closest structural homology to the VHR phosphatase. The structure, coupled with kinetic studies of site-directed mutants, identifies functionally important residues and reveals unique features, differentiating PRLs from other phosphatases. These differences include an unusually hydrophobic active site without the catalytically important serine/threonine found in most other phosphatases. The position of the general acid loop indicates the presence of conformational change upon catalysis. The studies also identify a potential regulatory role of Cys(49) that forms an intramolecular disulfide bond with the catalytic Cys(104) even under mildly reducing conditions. Molecular modeling of the highly homologous PRL-1 and PRL-2 phosphatases revealed unique surface elements that are potentially important for specificity.

Selected figure(s)

Figure 1.
FIG. 1. Structure of PRL-3. A, stereo view of the backbone superposition of the 20 lowest energy structures for residues Ala^8-Gln156. The unstructured N and C termini are not shown. B, ribbon representation of the average PRL-3 structure generated with MOLSCRIPT (41) and Raster3D (42). The secondary structure elements and N and C termini are labeled.

Figure 2.
FIG. 2. PRL phosphatases are highly homologous within their family but show low sequence similarity to the catalytic domains of other dual specificity phosphatases. The aligned phosphatases include human PRL-3 (gi:14589856), PRL-1 (gi:4506283), PRL-2 (gi:4506285), Drosophila PRL-1 (gi:3135665), worm PaRaLysed_cae (gi:17569857), human VHR (gi:181840), CDC14 (gi:34811075), PTEN (gi:1916328), and KAP (gi:443669). The secondary structural elements refer to PRL-3. The catalytic residues are shown in bold type.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 11882-11889) copyright 2004.

Figures were selected by an automated process.