2ifq

Crystal structure of S-nitroso thioredoxin

spinqualitylabelsall models 2ifq, resolution 1.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ifq is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EOH NonStd Res: SNC Related: 2hxk, 1ert Gene: TXN, TRDX, TRX, TRX1 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [THIO_HUMAN] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity. ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed We have determined the 1.65 A crystal structure of human thioredoxin-1 after treatment with S-nitrosoglutathione, providing a high-resolution view of this important protein modification and mechanistic insight into protein transnitrosation. Thioredoxin-1 appears to play an intermediary role in cellular S-nitrosylation and is important in numerous biological and pathobiological activities. S-Nitroso modifications of cysteines 62 and 69 are clearly visible in the structure and display planar cis geometries, whereas cysteines 32, 35, and 73 form intra- and intermolecular disulfide bonds. Surprisingly, the Cys 62 nitroso group is completely buried and pointing to the protein interior yet is the most readily formed at neutral pH. The Cys 69 nitroso group is also protected but requires a higher pH for stable formation. The helix intervening between residues 62 and 69 shifts by approximately 0.5 A to accommodate the SNO groups. The crystallographic asymmetric unit contains three independent molecules of thioredoxin, providing three views of the nitrosated protein. The three molecules are in general agreement but display subtle differences, including both cis and trans conformers for Cys 69 SNO in molecule C, and greater disorder in the Cys 62-Cys 69 helix in molecule B. Possible mechanisms for protein transnitrosation with specific geometric requirements and charge stabilization of the nitroxyl disulfide reaction intermediate are discussed. Buried S-nitrosocysteine revealed in crystal structures of human thioredoxin.,Weichsel A, Brailey JL, Montfort WR Biochemistry. 2007 Feb 6;46(5):1219-27. PMID:17260951 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thioredoxin

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