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==Crystal structure of human adenovirus 2 protease with a weak pyrimidine nitrile inhibitor==
==Crystal structure of human adenovirus 2 protease with a weak pyrimidine nitrile inhibitor==
<StructureSection load='4pid' size='340' side='right' caption='[[4pid]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
<StructureSection load='4pid' size='340' side='right'caption='[[4pid]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4pid]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ade02 Ade02]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PID OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PID FirstGlance]. <br>
<table><tr><td colspan='2'>[[4pid]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_adenovirus_2 Human adenovirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PID OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PID FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2UQ:N-BENZYL-2-[(Z)-IMINOMETHYL]PYRIMIDINE-5-CARBOXAMIDE'>2UQ</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2UQ:N-BENZYL-2-[(Z)-IMINOMETHYL]PYRIMIDINE-5-CARBOXAMIDE'>2UQ</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nln|1nln]], [[4pie|4pie]]</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=4pid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pid OCA], [https://pdbe.org/4pid PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pid RCSB], [https://www.ebi.ac.uk/pdbsum/4pid PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pid ProSAT]</span></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">L3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10515 ADE02])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenain Adenain], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.39 3.4.22.39] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pid OCA], [http://pdbe.org/4pid PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pid RCSB], [http://www.ebi.ac.uk/pdbsum/4pid PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pid ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/PRO_ADE02 PRO_ADE02]] Cleaves viral precursor proteins (pTP, pIIIa, pVI, pVII, pVIII, and pX) inside newly assembled particles giving rise to mature virions. Protease complexed to its cofactor slides along the viral DNA to specifically locate and cleave the viral precursors. Mature virions have a weakened organization compared to the unmature virions, thereby facilitating subsequent uncoating. Without maturation, the particle lacks infectivity and is unable to uncoat. Late in adenovirus infection, in the cytoplasm, may participate in the cytoskeleton destruction. Cleaves host cells cytoskeletal keratins K7 and K18.<ref>PMID:22791715</ref> [[http://www.uniprot.org/uniprot/CAP6_ADE02 CAP6_ADE02]] Pre-protein VI: During virus assembly, promotes hexon trimers nuclear import through nuclear pore complexes via an importin alpha/beta-dependent mechanism. By analogy to herpesviruses capsid assembly, might act as a scaffold protein to promote the formation of the icosahedral capsid.<ref>PMID:14633984</ref> <ref>PMID:15681401</ref> <ref>PMID:20333243</ref> <ref>PMID:20409568</ref> <ref>PMID:21209115</ref> <ref>PMID:21843868</ref>  Endosome lysis protein: Structural component of the virion that provides increased stability to the particle shell through its interaction with the core-capsid bridging protein. Fibers shedding during virus entry into host cell allows the endosome lysis protein to be exposed as a membrane-lytic peptide. Exhibits pH-independent membrane fragmentation activity and probably mediates viral rapid escape from host endosome via organellar membrane lysis. It is not clear if it then remains partially associated with the capsid and involved in the intracellular microtubule-dependent transport of capsid to the nucleus, or if it is lost during endosomal penetration.<ref>PMID:14633984</ref> <ref>PMID:15681401</ref> <ref>PMID:20333243</ref> <ref>PMID:20409568</ref> <ref>PMID:21209115</ref> <ref>PMID:21843868</ref>  Protease cofactor: Cofactor that activates the viral protease. Binds to viral protease in a 1:1 ratio.<ref>PMID:14633984</ref> <ref>PMID:15681401</ref> <ref>PMID:20333243</ref> <ref>PMID:20409568</ref> <ref>PMID:21209115</ref> <ref>PMID:21843868</ref> 
[https://www.uniprot.org/uniprot/PRO_ADE02 PRO_ADE02] Cleaves viral precursor proteins (pTP, pIIIa, pVI, pVII, pVIII, and pX) inside newly assembled particles giving rise to mature virions. Protease complexed to its cofactor slides along the viral DNA to specifically locate and cleave the viral precursors. Mature virions have a weakened organization compared to the unmature virions, thereby facilitating subsequent uncoating. Without maturation, the particle lacks infectivity and is unable to uncoat. Late in adenovirus infection, in the cytoplasm, may participate in the cytoskeleton destruction. Cleaves host cells cytoskeletal keratins K7 and K18.<ref>PMID:22791715</ref>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Ade02]]
[[Category: Human adenovirus 2]]
[[Category: Adenain]]
[[Category: Large Structures]]
[[Category: Altmann, E]]
[[Category: Altmann E]]
[[Category: Bernardi, A]]
[[Category: Bernardi A]]
[[Category: Combrink, K]]
[[Category: Combrink K]]
[[Category: Ellis, D]]
[[Category: Ellis D]]
[[Category: Erbel, P]]
[[Category: Erbel P]]
[[Category: Grosche, P]]
[[Category: Grosche P]]
[[Category: Hughes, N]]
[[Category: Hughes N]]
[[Category: Jarousse, N]]
[[Category: Jarousse N]]
[[Category: Melkko, S]]
[[Category: Mac Sweeney A]]
[[Category: Ramage, P]]
[[Category: Melkko S]]
[[Category: Sirockin, F]]
[[Category: Ramage P]]
[[Category: Sweeney, A Mac]]
[[Category: Sirockin F]]
[[Category: Adenovirus]]
[[Category: Cysteine protease]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Pvic cofactor]]
[[Category: Virus maturation]]

Revision as of 13:05, 1 February 2023

Crystal structure of human adenovirus 2 protease with a weak pyrimidine nitrile inhibitor

4pid, resolution 1.59Å

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