PDBsum entry 2mbc

Hydrolase

PDB id: 2mbc

Contents

Protein chain

162 a.a.

PDB id:

2mbc

Name:

Hydrolase

Title:

Solution structure of human holo-prl-3 in complex with vanadate

Structure:

Protein tyrosine phosphatase type iva 3. Chain: a. Fragment: unp residues 1-162. Synonym: prl-r, protein-tyrosine phosphatase 4a3, protein-tyrosine phosphatase of regenerating liver 3, prl-3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ptp4a3, prl3. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

K.Jeong,D.Kang,J.Kim,S.Shin,B.Jin,C.Lee,E.Kim,Y.H.Jeon,Y.Kim

Key ref:

K.W.Jeong et al. (2014). Structure and backbone dynamics of vanadate-bound PRL-3: comparison of 15N nuclear magnetic resonance relaxation profiles of free and vanadate-bound PRL-3. Biochemistry, 53, 4814-4825. PubMed id: 24983822 DOI: 10.1021/bi5003844

Date:

29-Jul-13 Release date: 09-Oct-13

Protein chain

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

Seq: 173 a.a.

Struc: 162 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: 10.1021/bi5003844

Biochemistry 53:4814-4825 (2014)

PubMed id: 24983822

Structure and backbone dynamics of vanadate-bound PRL-3: comparison of 15N nuclear magnetic resonance relaxation profiles of free and vanadate-bound PRL-3.

K.W.Jeong, D.I.Kang, E.Lee, A.Shin, B.Jin, Y.G.Park, C.K.Lee, E.H.Kim, Y.H.Jeon, E.E.Kim, Y.Kim.

ABSTRACT

Phosphatases of regenerating liver (PRLs) constitute a novel class of small, prenylated phosphatases with oncogenic activity. PRL-3 is particularly important in cancer metastasis and represents a potential therapeutic target. The flexibility of the WPD loop as well as the P-loop of protein tyrosine phosphatases is closely related to their catalytic activity. Using nuclear magnetic resonance spectroscopy, we studied the structure of vanadate-bound PRL-3, which was generated by addition of sodium orthovanadate to PRL-3. The WPD loop of free PRL-3 extended outside of the active site, forming an open conformation, whereas that of vanadate-bound PRL-3 was directed into the active site by a large movement, resulting in a closed conformation. We suggest that vanadate binding induced structural changes in the WPD loop, P-loop, helices α4-α6, and the polybasic region. Compared to free PRL-3, vanadate-bound PRL-3 has a longer α4 helix, where the catalytic R110 residue coordinates with vanadate in the active site. In addition, the hydrophobic cavity formed by helices α4-α6 with a depth of 14-15 Å can accommodate a farnesyl chain at the truncated prenylation motif of PRL-3, i.e., from R169 to M173. Conformational exchange data suggested that the WPD loop moves between open and closed conformations with a closing rate constant k(close) of 7 s(-1). This intrinsic loop flexibility of PRL-3 may be related to their catalytic rate and may play a role in substrate recognition.