View source for 4eno


==Crystal structure of oxidized human nm23-H1==
<StructureSection load='4eno' size='340' side='right'caption='[[4eno]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4eno]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ENO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ENO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4eno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eno OCA], [https://pdbe.org/4eno PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eno RCSB], [https://www.ebi.ac.uk/pdbsum/4eno PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eno ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NDKA_HUMAN 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.<ref>PMID:2056128</ref> <ref>PMID:8810265</ref> <ref>PMID:12628186</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:23519676</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4eno" style="background-color:#fffaf0;"></div>

==See Also==
*[[Nucleoside diphosphate kinase 3D structures|Nucleoside diphosphate kinase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kim M-S]]
[[Category: Shin D-H]]