View source for 3bbc

==Crystal structure of R88A mutant of the NM23-H2 transcription factor==
<StructureSection load='3bbc' size='340' side='right' caption='[[3bbc]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3bbc]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BBC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BBC FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nue|1nue]], [[3bbb|3bbb]], [[3bbf|3bbf]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NME2, NM23B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nucleoside-diphosphate_kinase Nucleoside-diphosphate kinase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bbc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bbc RCSB], [http://www.ebi.ac.uk/pdbsum/3bbc PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/NDKB_HUMAN NDKB_HUMAN]] Major role in the synthesis of nucleoside triphosphates other than ATP. Negatively regulates Rho activity by interacting with AKAP13/LBC. Acts as a transcriptional activator of the MYC gene; binds DNA non-specifically (PubMed:8392752). Exhibits histidine protein kinase activity.<ref>PMID:15249197</ref> <ref>PMID:20946858</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bb/3bbc_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The formation of G-quadruplex structures within the nuclease hypersensitive element (NHE) III(1) region of the c-myc promoter and the ability of these structures to repress c-myc transcription have been well established. However, just how these extremely stable DNA secondary structures are transformed to activate c-myc transcription is still unknown. NM23-H2/nucleoside diphosphate kinase B has been recognized as an activator of c-myc transcription via interactions with the NHE III(1) region of the c-myc gene promoter. Through the use of RNA interference, we confirmed the transcriptional regulatory role of NM23-H2. In addition, we find that further purification of NM23-H2 results in loss of the previously identified DNA strand cleavage activity, but retention of its DNA binding activity. NM23-H2 binds to both single-stranded guanine- and cytosine-rich strands of the c-myc NHE III(1) and, to a lesser extent, to a random single-stranded DNA template. However, it does not bind to or cleave the NHE III(1) in duplex form. Significantly, potassium ions and compounds that stabilize the G-quadruplex and i-motif structures have an inhibitory effect on NM23-H2 DNA-binding activity. Mutation of Arg(88) to Ala(88) (R88A) reduced both DNA and nucleotide binding but had minimal effect on the NM23-H2 crystal structure. On the basis of these data and molecular modeling studies, we have proposed a stepwise trapping-out of the NHE III(1) region in a single-stranded form, thus allowing single-stranded transcription factors to bind and activate c-myc transcription. Furthermore, this model provides a rationale for how the stabilization of the G-quadruplex or i-motif structures formed within the c-myc gene promoter region can inhibit NM23-H2 from activating c-myc gene expression. [Mol Cancer Ther 2009;8(5):1363-77].

NM23-H2 may play an indirect role in transcriptional activation of c-myc gene expression but does not cleave the nuclease hypersensitive element III1.,Dexheimer TS, Carey SS, Zuohe S, Gokhale VM, Hu X, Murata LB, Maes EM, Weichsel A, Sun D, Meuillet EJ, Montfort WR, Hurley LH Mol Cancer Ther. 2009 May 12. PMID:19435876<ref>PMID:19435876</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>

==See Also==
*[[Nucleoside diphosphate kinase|Nucleoside diphosphate kinase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Nucleoside-diphosphate kinase]]
[[Category: Montfort, W R]]
[[Category: Weichsel, A]]
[[Category: Activator]]
[[Category: Anti-oncogene]]
[[Category: Atp-binding]]
[[Category: Cancer]]
[[Category: Cell cycle]]
[[Category: Dna-binding]]
[[Category: Hexamer]]
[[Category: Kinase]]
[[Category: Magnesium]]
[[Category: Metal-binding]]
[[Category: Nm23 gen]]
[[Category: Nucleotide metabolism]]
[[Category: Nucleotide-binding]]
[[Category: Nucleus]]
[[Category: Phosphorylation]]
[[Category: Transcription regulation]]
[[Category: Transcriptional factor]]
[[Category: Transferase]]