1OEM

PTP1B with the catalytic cysteine oxidized to a sulfenyl-amide bond

Summary for 1OEM

• Entry DOI: 10.2210/pdb1oem/pdb
• Related: 1A5Y 1AAX 1BZC 1BZH 1BZJ 1C83 1C84 1C85 1C86 1C87 1C88 1ECV 1EEN 1EEO 1G1F 1G1G 1G1H 1G7F 1G7G 1GFY 1I57 1JF7 1KAK 1KAV 1L8G 1LQF 1N6W 1NL9 1NNY 1NO6 1NWL 1OEO 1OES 1OET 1OEU 1OEV 1PTT 1PTU 1PTV 1PTY 2HNP 2HNQ
• Descriptor: PROTEIN-TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 1 (2 entities in total)
• Functional Keywords: hydrolase, phosphorylation, phosphatase
• 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: 37365.64

Authors

Salmeen, A.,Andersen, J.N.,Myers, M.P.,Meng, T.C.,Hinks, J.A.,Tonks, N.K.,Barford, D. (deposition date: 2003-03-28, release date: 2003-06-12, Last modification date: 2023-12-13)

Primary citation

Salmeen, A.,Andersen, J.N.,Myers, M.P.,Meng, T.C.,Hinks, J.A.,Tonks, N.K.,Barford, D.
Redox Regulation of Protein Tyrosine Phosphatase Involves a Sulfenyl-Amide Intermediate
Nature, 423:769-, 2003

PubMed Abstract: The second messenger hydrogen peroxide is required for optimal activation of numerous signal transduction pathways, particularly those mediated by protein tyrosine kinases. One mechanism by which hydrogen peroxide regulates cellular processes is the transient inhibition of protein tyrosine phosphatases through the reversible oxidization of their catalytic cysteine, which suppresses protein dephosphorylation. Here we describe a structural analysis of the redox-dependent regulation of protein tyrosine phosphatase 1B (PTP1B), which is reversibly inhibited by oxidation after cells are stimulated with insulin and epidermal growth factor. The sulphenic acid intermediate produced in response to PTP1B oxidation is rapidly converted into a previously unknown sulphenyl-amide species, in which the sulphur atom of the catalytic cysteine is covalently linked to the main chain nitrogen of an adjacent residue. Oxidation of PTP1B to the sulphenyl-amide form is accompanied by large conformational changes in the catalytic site that inhibit substrate binding. We propose that this unusual protein modification both protects the active-site cysteine residue of PTP1B from irreversible oxidation to sulphonic acid and permits redox regulation of the enzyme by promoting its reversible reduction by thiols.

PubMed: 12802338
DOI: 10.1038/NATURE01680

Experimental method

X-RAY DIFFRACTION (1.8 Å)