3SME

Structure of PTP1B inactivated by H2O2/bicarbonate

Summary for 3SME

• Entry DOI: 10.2210/pdb3sme/pdb
• Descriptor: Tyrosine-protein phosphatase non-receptor type 1, MAGNESIUM ION (3 entities in total)
• Functional Keywords: hydrolase, sulfenyl amide bond between cys 215 and ser 216
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side: P18031
• Total number of polymer chains: 1
• Total formula weight: 34940.07

Authors

Tanner, J.J.,Singh, H. (deposition date: 2011-06-27, release date: 2011-10-19, Last modification date: 2024-11-20)

Primary citation

Zhou, H.,Singh, H.,Parsons, Z.D.,Lewis, S.M.,Bhattacharya, S.,Seiner, D.R.,Labutti, J.N.,Reilly, T.J.,Tanner, J.J.,Gates, K.S.
The Biological Buffer Bicarbonate/CO(2) Potentiates H(2)O(2)-Mediated Inactivation of Protein Tyrosine Phosphatases.
J.Am.Chem.Soc., 133:15803-15805, 2011

PubMed Abstract: Hydrogen peroxide is a cell signaling agent that inactivates protein tyrosine phosphatases (PTPs) via oxidation of their catalytic cysteine residue. PTPs are inactivated rapidly during H(2)O(2)-mediated cellular signal transduction processes, but, paradoxically, hydrogen peroxide is a rather sluggish PTP inactivator in vitro. Here we present evidence that the biological buffer bicarbonate/CO(2) potentiates the ability of H(2)O(2) to inactivate PTPs. The results of biochemical experiments and high-resolution crystallographic analysis are consistent with a mechanism involving oxidation of the catalytic cysteine residue by peroxymonocarbonate generated via the reaction of H(2)O(2) with HCO(3)(-)/CO(2).

PubMed: 21913686
DOI: 10.1021/ja2077137

Experimental method

X-RAY DIFFRACTION (1.7 Å)