3EU0

Crystal structure of the S-nitrosylated Cys215 of PTP1B

Summary for 3EU0

• Entry DOI: 10.2210/pdb3eu0/pdb
• Descriptor: Tyrosine-protein phosphatase non-receptor type 1 (2 entities in total)
• Functional Keywords: s-nitrosylated protein, hydrolase, acetylation, endoplasmic reticulum, membrane, oxidation, phosphoprotein, polymorphism, protein 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: 38223.51

Authors

Chu, H.M.,Wang, A.H.J.,Chen, Y.Y.,Pan, K.T.,Wang, D.L.,Khoo, K.H.,Meng, T.C. (deposition date: 2008-10-09, release date: 2008-11-11, Last modification date: 2024-11-06)

Primary citation

Chen, Y.Y.,Chu, H.M.,Pan, K.T.,Teng, C.H.,Wang, D.L.,Wang, A.H.,Khoo, K.H.,Meng, T.C.
Cysteine S-Nitrosylation Protects Protein-tyrosine Phosphatase 1B against Oxidation-induced Permanent Inactivation
J.Biol.Chem., 283:35265-35272, 2008

PubMed Abstract: Protein S-nitrosylation mediated by cellular nitric oxide (NO) plays a primary role in executing biological functions in cGMP-independent NO signaling. Although S-nitrosylation appears similar to Cys oxidation induced by reactive oxygen species, the molecular mechanism and biological consequence remain unclear. We investigated the structural process of S-nitrosylation of protein-tyrosine phosphatase 1B (PTP1B). We treated PTP1B with various NO donors, including S-nitrosothiol reagents and compound-releasing NO radicals, to produce site-specific Cys S-nitrosylation identified using advanced mass spectrometry (MS) techniques. Quantitative MS showed that the active site Cys-215 was the primary residue susceptible to S-nitrosylation. The crystal structure of NO donor-reacted PTP1B at 2.6 A resolution revealed that the S-NO state at Cys-215 had no discernible irreversibly oxidized forms, whereas other Cys residues remained in their free thiol states. We further demonstrated that S-nitrosylation of the Cys-215 residue protected PTP1B from subsequent H(2)O(2)-induced irreversible oxidation. Increasing the level of cellular NO by pretreating cells with an NO donor or by activating ectopically expressed NO synthase inhibited reactive oxygen species-induced irreversible oxidation of endogenous PTP1B. These findings suggest that S-nitrosylation might prevent PTPs from permanent inactivation caused by oxidative stress.

PubMed: 18840608
DOI: 10.1074/jbc.M805287200

Experimental method

X-RAY DIFFRACTION (2.7 Å)