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| | <StructureSection load='2hvd' size='340' side='right'caption='[[2hvd]], [[Resolution|resolution]] 2.15Å' scene=''> | | <StructureSection load='2hvd' size='340' side='right'caption='[[2hvd]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2hvd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HVD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2hvd]] is a 3 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=2HVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HVD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2hve|2hve]], [[1ucn|1ucn]], [[1jxv|1jxv]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NME1, NDPKA, NM23 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Nucleoside-diphosphate_kinase Nucleoside-diphosphate kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.6 2.7.4.6] </span></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=2hvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hvd OCA], [https://pdbe.org/2hvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hvd RCSB], [https://www.ebi.ac.uk/pdbsum/2hvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hvd ProSAT]</span></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=2hvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hvd OCA], [https://pdbe.org/2hvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hvd RCSB], [https://www.ebi.ac.uk/pdbsum/2hvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hvd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hv/2hvd_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hv/2hvd_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nucleoside-diphosphate kinase]]
| + | [[Category: Dautant A]] |
| - | [[Category: Dautant, A]] | + | [[Category: Georgescauld F]] |
| - | [[Category: Georgescauld, F]] | + | [[Category: Giraud M-F]] |
| - | [[Category: Giraud, M F]] | + | [[Category: Lascu I]] |
| - | [[Category: Lascu, I]] | + | |
| - | [[Category: Complex adp]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
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.[1] [2] [3]
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
Nm23 was the first metastasis suppressor gene identified. This gene encodes a NDP kinase that also exhibits other properties like histidine protein kinase and interactions with proteins and DNA. The S120G mutant of NDPK-A has been identified in aggressive neuroblastomas and has been found to reduce the metastasis suppressor effect of Nm23. In order to understand the differences between the wild type and the S120G mutant, we have determined the structure of both mutant and wild type NDPK-A in complex with ADP. Our results reveal that there are no significant changes between the two enzyme versions even in the surroundings of the catalytic histidine that is required for NDP kinase activity. This suggests that the S120G mutation may affect an other protein property than NDP kinase activity.
Crystal structures of S120G mutant and wild type of human nucleoside diphosphate kinase A in complex with ADP.,Giraud MF, Georgescauld F, Lascu I, Dautant A J Bioenerg Biomembr. 2006 Aug;38(3-4):261-4. Epub 2006 Sep 1. PMID:16944299[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hailat N, Keim DR, Melhem RF, Zhu XX, Eckerskorn C, Brodeur GM, Reynolds CP, Seeger RC, Lottspeich F, Strahler JR, et al.. High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification. J Clin Invest. 1991 Jul;88(1):341-5. PMID:2056128 doi:http://dx.doi.org/10.1172/JCI115299
- ↑ MacDonald NJ, Freije JM, Stracke ML, Manrow RE, Steeg PS. Site-directed mutagenesis of nm23-H1. Mutation of proline 96 or serine 120 abrogates its motility inhibitory activity upon transfection into human breast carcinoma cells. J Biol Chem. 1996 Oct 11;271(41):25107-16. PMID:8810265
- ↑ Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J. Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Cell. 2003 Mar 7;112(5):659-72. PMID:12628186
- ↑ Giraud MF, Georgescauld F, Lascu I, Dautant A. Crystal structures of S120G mutant and wild type of human nucleoside diphosphate kinase A in complex with ADP. J Bioenerg Biomembr. 2006 Aug;38(3-4):261-4. Epub 2006 Sep 1. PMID:16944299 doi:10.1007/s10863-006-9043-0
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