3I7Z

Protein Tyrosine Phosphatase 1B - Transition state analog for the first catalytic step

Summary for 3I7Z

• Entry DOI: 10.2210/pdb3i7z/pdb
• Related: 1A5Y 1PTU 2CM2 2HNQ 3I80
• Descriptor: Tyrosine-protein phosphatase non-receptor type 1, EGFR receptor fragment, VANADATE ION, ... (6 entities in total)
• Functional Keywords: hydrolase, p-loop, wpd-loop, protein phosphatase, egfr receptor, vanadate, acetylation, endoplasmic reticulum, membrane, oxidation, phosphoprotein, polymorphism
• Biological source: Homo sapiens (human); More
• Cellular location: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side: P18031
• Total number of polymer chains: 2
• Total formula weight: 38633.76

Authors

Brandao, T.A.S.,Johnson, S.J.,Hengge, A.C. (deposition date: 2009-07-09, release date: 2010-03-16, Last modification date: 2023-09-06)

Primary citation

Brandao, T.A.,Hengge, A.C.,Johnson, S.J.
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, 2010

PubMed 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.

PubMed: 20236928
DOI: 10.1074/jbc.M109.066951

Experimental method

X-RAY DIFFRACTION (2.3 Å)