2brk: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2brk.png|left|200px]]
+==CRYSTAL STRUCTURE OF HEPATITIS C VIRUS POLYMERASE IN COMPLEX WITH AN ALLOSTERIC INHIBITOR (COMPOUND 1)==
+<StructureSection load='2brk' size='340' side='right' caption='[[2brk]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2brk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BRK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BRK FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CMF:3-CYCLOHEXYL-1-(2-MORPHOLIN-4-YL-2-OXOETHYL)-2-PHENYL-1H-INDOLE-6-CARBOXYLIC+ACID'>CMF</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1a1q|1a1q]], [[1c2p|1c2p]], [[1csj|1csj]], [[1cu1|1cu1]], [[1gx5|1gx5]], [[1gx6|1gx6]], [[1jxp|1jxp]], [[1ns3|1ns3]], [[1quv|1quv]], [[2brl|2brl]], [[8ohm|8ohm]]</td></tr>
+<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2brk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2brk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2brk RCSB], [http://www.ebi.ac.uk/pdbsum/2brk PDBsum]</span></td></tr>
+<table>
+== 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/br/2brk_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 hepatitis C virus (HCV) polymerase is required for replication of the viral genome and is a key target for therapeutic intervention against HCV. We have determined the crystal structures of the HCV polymerase complexed with two indole-based allosteric inhibitors at 2.3- and 2.4-Angstroms resolution. The structures show that these inhibitors bind to a site on the surface of the thumb domain. A cyclohexyl and phenyl ring substituents, bridged by an indole moiety, fill two closely spaced pockets, whereas a carboxylate substituent forms a salt bridge with an exposed arginine side chain. Interestingly, in the apoenzyme, the inhibitor binding site is occupied by a small alpha-helix at the tip of the N-terminal loop that connects the fingers and thumb domains. Thus, these molecules inhibit the enzyme by preventing formation of intramolecular contacts between these two domains and consequently precluding their coordinated movements during RNA synthesis. Our structures identify a novel mechanism by which a new class of allosteric inhibitors inhibits the HCV polymerase and open the way to the development of novel antiviral agents against this clinically relevant human pathogen.
-{{STRUCTURE_2brk|  PDB=2brk  |  SCENE=  }}
+Interdomain communication in hepatitis C virus polymerase abolished by small molecule inhibitors bound to a novel allosteric site.,Di Marco S, Volpari C, Tomei L, Altamura S, Harper S, Narjes F, Koch U, Rowley M, De Francesco R, Migliaccio G, Carfi A J Biol Chem. 2005 Aug 19;280(33):29765-70. Epub 2005 Jun 13. PMID:15955819<ref>PMID:15955819</ref>
-===CRYSTAL STRUCTURE OF HEPATITIS C VIRUS POLYMERASE IN COMPLEX WITH AN ALLOSTERIC INHIBITOR (COMPOUND 1)===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_15955819}}
-==About this Structure==
-[[2brk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BRK OCA].
 ==See Also==
 *[[RNA polymerase|RNA polymerase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:015955819</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Hepatitis c virus]]
 [[Category: RNA-directed RNA polymerase]]