1OES
Oxidation state of protein tyrosine phosphatase 1B
Summary for 1OES
| Entry DOI | 10.2210/pdb1oes/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 1OEM 1OEO 1OET 1OEU 1OEV 1PTT 1PTU 1PTV 1PTY 2HNP 2HNQ |
| Descriptor | PROTEIN-TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 1, MAGNESIUM ION (3 entities in total) |
| Functional Keywords | hydrolase, protein tyrosine phosphatase, oxidative regulation, phosphorylation |
| 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 | 37389.94 |
| Authors | van Montfort, R.L.M.,Congreve, M.,Tisi, D.,Carr, R.,Jhoti, H. (deposition date: 2003-03-31, release date: 2003-06-12, Last modification date: 2023-12-13) |
| Primary citation | van Montfort, R.L.,Congreve, M.,Tisi, D.,Carr, R.,Jhoti, H. Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B. Nature, 423:773-777, 2003 Cited by PubMed Abstract: Protein tyrosine phosphatases regulate signal transduction pathways involving tyrosine phosphorylation and have been implicated in the development of cancer, diabetes, rheumatoid arthritis and hypertension. Increasing evidence suggests that the cellular redox state is involved in regulating tyrosine phosphatase activity through the reversible oxidization of the catalytic cysteine to sulphenic acid (Cys-SOH). But how further oxidation to the irreversible sulphinic (Cys-SO2H) and sulphonic (Cys-SO3H) forms is prevented remains unclear. Here we report the crystal structures of the regulatory sulphenic and irreversible sulphinic and sulphonic acids of protein tyrosine phosphatase 1B (PTP1B), an important enzyme in the negative regulation of the insulin receptor and a therapeutic target in type II diabetes and obesity. We also identify a sulphenyl-amide species that is formed through oxidation of its catalytic cysteine. Formation of the sulphenyl-amide causes large changes in the PTP1B active site, which are reversible by reduction with the cellular reducing agent glutathione. The sulphenyl-amide is a protective intermediate in the oxidative inhibition of PTP1B. In addition, it may facilitate reactivation of PTP1B by biological thiols and signal a unique state of the protein. PubMed: 12802339DOI: 10.1038/nature01681 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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