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1f3f

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[[Image:1f3f.jpg|left|200px]]<br /><applet load="1f3f" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1f3f, resolution 1.85&Aring;" />
 
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'''STRUCTURE OF THE H122G NUCLEOSIDE DIPHOSPHATE KINASE / D4T-TRIPHOSPHATE.MG COMPLEX'''<br />
 
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==Overview==
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==STRUCTURE OF THE H122G NUCLEOSIDE DIPHOSPHATE KINASE / D4T-TRIPHOSPHATE.MG COMPLEX==
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AIDS chemotherapy is limited by inadequate intracellular concentrations of, the active triphosphate form of nucleoside analogues, leading to, incomplete inhibition of viral replication and the appearance of, drug-resistant virus. Drug activation by nucleoside diphosphate kinase and, inhibition of HIV-1 reverse transcriptase were studied comparatively. We, synthesized analogues with a borano (BH(3)(-)) group on the, alpha-phosphate, and found that they are substrates for both enzymes., X-ray structures of complexes with nucleotide diphosphate kinase provided, a structural basis for their activation. The complex with d4T triphosphate, displayed an intramolecular CH.O bond contributing to catalysis, and the, R(p) diastereoisomer of thymidine alpha-boranotriphosphate bound like a, normal substrate. Using alpha-(R(p))-boranophosphate derivatives of the, clinically relevant compounds AZT and d4T, the presence of the, alpha-borano group improved both phosphorylation by nucleotide diphosphate, kinase and inhibition of reverse transcription. Moreover, repair of, blocked DNA chains by pyrophosphorolysis was reduced significantly in, variant reverse transcriptases bearing substitutions found in, drug-resistant viruses. Thus, the alpha-borano modification of analogues, targeting reverse transcriptase may be of generic value in fighting viral, drug resistance.
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<StructureSection load='1f3f' size='340' side='right'caption='[[1f3f]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1f3f]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F3F FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D4D:2,3-DEHYDRO-2,3-DEOXY-THYMIDINE+5-DIPHOSPHATE'>D4D</scene>, <scene name='pdbligand=D4T:2,3-DEHYDRO-2,3-DEOXY-THYMIDINE+5-TRIPHOSPHATE'>D4T</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1f3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f3f OCA], [https://pdbe.org/1f3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f3f RCSB], [https://www.ebi.ac.uk/pdbsum/1f3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f3f ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NDKC_DICDI NDKC_DICDI]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f3/1f3f_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/main_output.php?pdb_ID=1f3f ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1F3F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum] with <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=D4T:'>D4T</scene> and <scene name='pdbligand=D4D:'>D4D</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F3F OCA].
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*[[Nucleoside diphosphate kinase 3D structures|Nucleoside diphosphate kinase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Structural basis for activation of alpha-boranophosphate nucleotide analogues targeting drug-resistant reverse transcriptase., Meyer P, Schneider B, Sarfati S, Deville-Bonne D, Guerreiro C, Boretto J, Janin J, Veron M, Canard B, EMBO J. 2000 Jul 17;19(14):3520-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10899107 10899107]
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[[Category: Dictyostelium discoideum]]
[[Category: Dictyostelium discoideum]]
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[[Category: Nucleoside-diphosphate kinase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Boretto J]]
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[[Category: Boretto, J.]]
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[[Category: Canard B]]
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[[Category: Canard, B.]]
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[[Category: Deville-Bonne D]]
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[[Category: Deville-Bonne, D.]]
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[[Category: Guerreiro C]]
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[[Category: Guerreiro, C.]]
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[[Category: Janin J]]
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[[Category: Janin, J.]]
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[[Category: Meyer P]]
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[[Category: Meyer, P.]]
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[[Category: Sarfati S]]
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[[Category: Sarfati, S.]]
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[[Category: Schneider B]]
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[[Category: Schneider, B.]]
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[[Category: Veron M]]
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[[Category: Veron, M.]]
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[[Category: D4D]]
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[[Category: D4T]]
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[[Category: MG]]
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[[Category: PO4]]
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[[Category: anti-hiv nucleoside analogue]]
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[[Category: ch...o bond]]
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[[Category: nucleoside diphosphate kinase]]
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[[Category: phosphorylation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:45:37 2008''
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Current revision

STRUCTURE OF THE H122G NUCLEOSIDE DIPHOSPHATE KINASE / D4T-TRIPHOSPHATE.MG COMPLEX

PDB ID 1f3f

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