4eno

Crystal structure of oxidized human nm23-H1

spinqualitylabelsall models 4eno, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4eno is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NDKA_HUMAN Major role in the synthesis of nucleoside triphosphates other than ATP. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities. Involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination. Publication Abstract from PubMed Nm23-H1/NDPK-A, a tumour metastasis suppressor, is a multifunctional housekeeping enzyme with nucleoside diphosphate kinase activity. Hexameric Nm23-H1 is required for suppression of tumour metastasis and it is dissociated into dimers under oxidative conditions. Here, the crystal structure of oxidized Nm23-H1 is presented. It reveals the formation of an intramolecular disulfide bond between Cys4 and Cys145 that triggers a large conformational change that destabilizes the hexameric state. The dependence of the dissociation dynamics on the H2O2 concentration was determined using hydrogen/deuterium-exchange experiments. The quaternary conformational change provides a suitable environment for the oxidation of Cys109 to sulfonic acid, as demonstrated by peptide sequencing using nanoUPLC-ESI-q-TOF tandem MS. From these and other data, it is proposed that the molecular and cellular functions of Nm23-H1 are regulated by a series of oxidative modifications coupled to its oligomeric states and that the modified cysteines are resolvable by NADPH-dependent reduction systems. These findings broaden the understanding of the complicated enzyme-regulatory mechanisms that operate under oxidative conditions. Structure of Nm23-H1 under oxidative conditions.,Kim MS, Jeong J, Jeong J, Shin DH, Lee KJ Acta Crystallogr D Biol Crystallogr. 2013 Apr;69(Pt 4):669-80. doi:, 10.1107/S0907444913001194. Epub 2013 Mar 14. PMID:23519676 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nucleoside diphosphate kinase 3D structures

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