1mn9: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
(14 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1mn9.gif|left|200px]]
<!--
The line below this paragraph, containing "STRUCTURE_1mn9", creates the "Structure Box" on the page.
You may change the PDB parameter (which sets the PDB file loaded into the applet)
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
or leave the SCENE parameter empty for the default display.
-->
{{STRUCTURE_1mn9|  PDB=1mn9  |  SCENE=  }}
'''NDP kinase mutant (H122G) complex with RTP'''


==NDP kinase mutant (H122G) complex with RTP==
<StructureSection load='1mn9' size='340' side='right'caption='[[1mn9]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1mn9]] 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=1MN9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MN9 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RTP:RIBAVIRIN+TRIPHOSPHATE'>RTP</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=1mn9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mn9 OCA], [https://pdbe.org/1mn9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mn9 RCSB], [https://www.ebi.ac.uk/pdbsum/1mn9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mn9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NDKC_DICDI NDKC_DICDI]
== 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/mn/1mn9_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/main_output.php?pdb_ID=1mn9 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ribavirin used in therapies against hepatitis C virus (HCV) is potentially efficient against other viruses but presents a high cytotoxicity. Several ribavirin triphosphate analogs modified on the ribose moiety were synthesized and tested in vitro on the RNA polymerases of HCV, phage T7, and HIV-1 reverse transcriptase. Modified nucleotides with 2'-deoxy, 3'-deoxy, 2',3'-dideoxy, 2',3'-dideoxy-2',3'-dehydro, and 2',3'-epoxy-ribose inhibited the HCV enzyme but not the other two polymerases. They were also analyzed as substrates for nucleoside diphosphate (NDP) kinase, the enzyme responsible for the last step of the cellular activation of antiviral nucleoside analogs. An X-ray structure of NDP kinase complexed with ribavirin triphosphate was determined. It demonstrates that the analog binds as a normal substrate despite the modified base and confirms the crucial role of the 3'-hydroxyl group in the phosphorylation reaction. The 3'-hydroxyl is required for inhibition of the initiation step of RNA synthesis by HCV polymerase, and both sugar hydroxyls must be present to inhibit elongation. The 2'deoxyribavirin is the only derivative efficient in vitro against HCV polymerase and properly activated by NDP kinase.


==Overview==
Structural analysis of the activation of ribavirin analogs by NDP kinase: comparison with other ribavirin targets.,Gallois-Montbrun S, Chen Y, Dutartre H, Sophys M, Morera S, Guerreiro C, Schneider B, Mulard L, Janin J, Veron M, Deville-Bonne D, Canard B Mol Pharmacol. 2003 Mar;63(3):538-46. PMID:12606760<ref>PMID:12606760</ref>
Ribavirin used in therapies against hepatitis C virus (HCV) is potentially efficient against other viruses but presents a high cytotoxicity. Several ribavirin triphosphate analogs modified on the ribose moiety were synthesized and tested in vitro on the RNA polymerases of HCV, phage T7, and HIV-1 reverse transcriptase. Modified nucleotides with 2'-deoxy, 3'-deoxy, 2',3'-dideoxy, 2',3'-dideoxy-2',3'-dehydro, and 2',3'-epoxy-ribose inhibited the HCV enzyme but not the other two polymerases. They were also analyzed as substrates for nucleoside diphosphate (NDP) kinase, the enzyme responsible for the last step of the cellular activation of antiviral nucleoside analogs. An X-ray structure of NDP kinase complexed with ribavirin triphosphate was determined. It demonstrates that the analog binds as a normal substrate despite the modified base and confirms the crucial role of the 3'-hydroxyl group in the phosphorylation reaction. The 3'-hydroxyl is required for inhibition of the initiation step of RNA synthesis by HCV polymerase, and both sugar hydroxyls must be present to inhibit elongation. The 2'deoxyribavirin is the only derivative efficient in vitro against HCV polymerase and properly activated by NDP kinase.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1MN9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MN9 OCA].
</div>
<div class="pdbe-citations 1mn9" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structural analysis of the activation of ribavirin analogs by NDP kinase: comparison with other ribavirin targets., Gallois-Montbrun S, Chen Y, Dutartre H, Sophys M, Morera S, Guerreiro C, Schneider B, Mulard L, Janin J, Veron M, Deville-Bonne D, Canard B, Mol Pharmacol. 2003 Mar;63(3):538-46. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12606760 12606760]
*[[Nucleoside diphosphate kinase 3D structures|Nucleoside diphosphate kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dictyostelium discoideum]]
[[Category: Dictyostelium discoideum]]
[[Category: Nucleoside-diphosphate kinase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Canard B]]
[[Category: Canard, B.]]
[[Category: Chen Y]]
[[Category: Chen, Y.]]
[[Category: Deville-bonne D]]
[[Category: Deville-bonne, D.]]
[[Category: Dutartre H]]
[[Category: Dutartre, H.]]
[[Category: Gallois-montbrun S]]
[[Category: Gallois-montbrun, S.]]
[[Category: Guerreiro C]]
[[Category: Guerreiro, C.]]
[[Category: Janin J]]
[[Category: Janin, J.]]
[[Category: Morera S]]
[[Category: Morera, S.]]
[[Category: Mulard L]]
[[Category: Mulard, L.]]
[[Category: Schneider B]]
[[Category: Schneider, B.]]
[[Category: Veron M]]
[[Category: Veron, M.]]
[[Category: Ndp kinase-ribavirin complex]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 01:26:59 2008''

Latest revision as of 18:14, 29 May 2024

NDP kinase mutant (H122G) complex with RTP

1mn9, resolution 2.90Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=1mn9&oldid=4172548"