PDBsum entry 3i7z

Hydrolase

PDB id: 3i7z

Contents

Protein chain

297 a.a. *

Ligands

ASP-ALA-ASP-GLU-TYR-LEU

VO4

TRS ×2

GOL ×2

Waters ×150

* Residue conservation analysis

PDB id:

3i7z

Name:

Hydrolase

Title:

Protein tyrosine phosphatase 1b - transition state analog for the first catalytic step

Structure:

Tyrosine-protein phosphatase non-receptor type 1. Chain: a. Fragment: residues 1-321. Synonym: protein-tyrosine phosphatase 1b, ptp-1b. Engineered: yes. Egfr receptor fragment. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ptp1b, ptpn1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.30Å R-factor: 0.207 R-free: 0.233

Authors:

T.A.S.Brandao,S.J.Johnson,A.C.Hengge

Key ref:

T.A.Brandão et al. (2010). Insights into the reaction of protein-tyrosine phosphatase 1B: crystal structures for transition state analogs of both catalytic steps. J Biol Chem, 285, 15874-15883. PubMed id: 20236928

Date:

09-Jul-09 Release date: 16-Mar-10

Protein chain

P18031  (PTN1_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 1 from Homo sapiens

Seq: 435 a.a.

Struc: 297 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

J Biol Chem 285:15874-15883 (2010)

PubMed id: 20236928

Insights into the reaction of protein-tyrosine phosphatase 1B: crystal structures for transition state analogs of both catalytic steps.

T.A.Brandão, A.C.Hengge, S.J.Johnson.

ABSTRACT

Catalysis by protein-tyrosine phosphatase 1B (PTP1B) occurs through a two-step mechanism involving a phosphocysteine intermediate. We have solved crystal structures for the transition state analogs for both steps. Together with previously reported crystal structures of apo-PTP1B, the Michaelis complex of an inactive mutant, the phosphoenzyme intermediate, and the product complex, a full picture of all catalytic steps can now be depicted. The transition state analog for the first catalytic step comprises a ternary complex between the catalytic cysteine of PTP1B, vanadate, and the peptide DADEYL, a fragment of a physiological substrate. The equatorial vanadate oxygen atoms bind to the P-loop, and the apical positions are occupied by the peptide tyrosine oxygen and by the PTP1B cysteine sulfur atom. The vanadate assumes a trigonal bipyramidal geometry in both transition state analog structures, with very similar apical O-O distances, denoting similar transition states for both phosphoryl transfer steps. Detailed interactions between the flanking peptide and the enzyme are discussed.