3sj8: Difference between revisions
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[[ | ==Crystal structure of the 3C protease from coxsackievirus A16== | ||
<StructureSection load='3sj8' size='340' side='right' caption='[[3sj8]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3sj8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_coxsackievirus_a16 Human coxsackievirus a16]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SJ8 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cqq|1cqq]], [[2zty|2zty]], [[1l1n|1l1n]], [[3sj9|3sj9]], [[3sji|3sji]], [[3sjk|3sjk]], [[3sjo|3sjo]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31704 Human coxsackievirus A16])</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </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=3sj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sj8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sj8 RCSB], [http://www.ebi.ac.uk/pdbsum/3sj8 PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the major causative agents of hand foot and mouth disease (HFMD) which is prevalent in Asia. Thus far there are no prophylactic or therapeutic measures against HFMD. The 3C proteases from EV71 and CVA16 play important roles in viral replication and are therefore ideal drug targets. By using biochemical, mutational and structural approaches, we broadly characterized both proteases. A series of high-resolution structures of the free or substrate-bound enzymes were solved. These structures, together with our cleavage specificity assay, well explain the marked substrate preferences of both proteases for particular P4, P1 and P1' residue types, as well as their relative malleability for P2 amino acid. More importantly, the complex structures of EV71 and CVA16 3Cs with Rupintrivir, a specific human rhinovirus (HRV) 3C protease inhibitor, were solved. These structures reveal a half-closed S2 subsite and a size-reduced S1' subsite that limit the access of the P1' group of Rupitrivir to both enzymes, explaining the reported low inhibition activity of the compound toward EV71 and CVA16. In conclusion, the detailed characterization of both proteases in this study could direct us for a proposal of rational design of EV71/CVA16 3C inhibitors. | |||
Enterovirus 71 and Coxsackievirus A16 3C proteases: binding to Rupintrivir and their substrate, and anti-HFMD drug design.,Lu G, Qi J, Chen Z, Xu X, Gao F, Lin D, Qian W, Liu H, Jiang H, Yan J, Gao GF J Virol. 2011 Jul 27. PMID:21795339<ref>PMID:21795339</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
< | |||
[[Category: Human coxsackievirus a16]] | [[Category: Human coxsackievirus a16]] | ||
[[Category: Picornain 3C]] | [[Category: Picornain 3C]] | ||
Revision as of 08:27, 5 June 2014
Crystal structure of the 3C protease from coxsackievirus A16Crystal structure of the 3C protease from coxsackievirus A16
Structural highlights
Publication Abstract from PubMedEnterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the major causative agents of hand foot and mouth disease (HFMD) which is prevalent in Asia. Thus far there are no prophylactic or therapeutic measures against HFMD. The 3C proteases from EV71 and CVA16 play important roles in viral replication and are therefore ideal drug targets. By using biochemical, mutational and structural approaches, we broadly characterized both proteases. A series of high-resolution structures of the free or substrate-bound enzymes were solved. These structures, together with our cleavage specificity assay, well explain the marked substrate preferences of both proteases for particular P4, P1 and P1' residue types, as well as their relative malleability for P2 amino acid. More importantly, the complex structures of EV71 and CVA16 3Cs with Rupintrivir, a specific human rhinovirus (HRV) 3C protease inhibitor, were solved. These structures reveal a half-closed S2 subsite and a size-reduced S1' subsite that limit the access of the P1' group of Rupitrivir to both enzymes, explaining the reported low inhibition activity of the compound toward EV71 and CVA16. In conclusion, the detailed characterization of both proteases in this study could direct us for a proposal of rational design of EV71/CVA16 3C inhibitors. Enterovirus 71 and Coxsackievirus A16 3C proteases: binding to Rupintrivir and their substrate, and anti-HFMD drug design.,Lu G, Qi J, Chen Z, Xu X, Gao F, Lin D, Qian W, Liu H, Jiang H, Yan J, Gao GF J Virol. 2011 Jul 27. PMID:21795339[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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