2op9

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "2op9" [edit=sysop:move=sysop])
Line 1: Line 1:
-
[[Image:2op9.png|left|200px]]
+
==Substrate Specificity Profiling and Identification of a New Class of Inhibitor for the Major Protease of the SARS Coronavirus==
 +
<StructureSection load='2op9' size='340' side='right' caption='[[2op9]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2op9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OP9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2OP9 FirstGlance]. <br>
 +
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=WR1:NALPHA-[(BENZYLOXY)CARBONYL]-N-[(1R)-4-HYDROXY-1-METHYL-2-OXOBUTYL]-L-PHENYLALANINAMIDE'>WR1</scene><br>
 +
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">3Clpro ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 SARS coronavirus])</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=2op9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2op9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2op9 RCSB], [http://www.ebi.ac.uk/pdbsum/2op9 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/op/2op9_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 ==
 +
Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a high rate of mortality. The SARS-associated coronavirus (SARS-CoV) has been identified as the etiological agent of the disease. Although public health procedures have been effective in combating the spread of SARS, concern remains about the possibility of a recurrence. Various approaches are being pursued for the development of efficacious therapeutics. One promising approach is to develop small molecule inhibitors of the essential major polyprotein processing protease 3Clpro. Here we report a complete description of the tetrapeptide substrate specificity of 3Clpro using fully degenerate peptide libraries consisting of all 160,000 possible naturally occurring tetrapeptides. The substrate specificity data show the expected P1-Gln P2-Leu specificity and elucidate a novel preference for P1-His containing substrates equal to the expected preference for P1-Gln. These data were then used to develop optimal substrates for a high-throughput screen of a 2000 compound small-molecule inhibitor library consisting of known cysteine protease inhibitor scaffolds. We also report the 1.8 A X-ray crystal structure of 3Clpro bound to an irreversible inhibitor. This inhibitor, an alpha,beta-epoxyketone, inhibits 3Clpro with a k3/Ki of 0.002 microM(-1) s(-1) in a mode consistent with the substrate specificity data. Finally, we report the successful rational improvement of this scaffold with second generation inhibitors. These data provide the foundation for a rational small-molecule inhibitor design effort based upon the inhibitor scaffold identified, the crystal structure of the complex, and a more complete understanding of P1-P4 substrate specificity.
-
{{STRUCTURE_2op9| PDB=2op9 | SCENE= }}
+
Substrate specificity profiling and identification of a new class of inhibitor for the major protease of the SARS coronavirus.,Goetz DH, Choe Y, Hansell E, Chen YT, McDowell M, Jonsson CB, Roush WR, McKerrow J, Craik CS Biochemistry. 2007 Jul 31;46(30):8744-52. Epub 2007 Jul 3. PMID:17605471<ref>PMID:17605471</ref>
-
===Substrate Specificity Profiling and Identification of a New Class of Inhibitor for the Major Protease of the SARS Coronavirus===
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
 
+
</div>
-
{{ABSTRACT_PUBMED_17605471}}
+
== References ==
-
 
+
<references/>
-
==About this Structure==
+
__TOC__
-
[[2op9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OP9 OCA].
+
</StructureSection>
-
 
+
-
==Reference==
+
-
<ref group="xtra">PMID:017605471</ref><references group="xtra"/>
+
[[Category: Sars coronavirus]]
[[Category: Sars coronavirus]]
[[Category: Craik, C S.]]
[[Category: Craik, C S.]]

Revision as of 19:23, 30 September 2014

Substrate Specificity Profiling and Identification of a New Class of Inhibitor for the Major Protease of the SARS Coronavirus

2op9, resolution 1.80Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2op9"
Views
Personal tools
Navigation
Toolbox