7ara
From Proteopedia
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==Rhinovirus A2 2A protease in complex with zVAM.fmk== | ==Rhinovirus A2 2A protease in complex with zVAM.fmk== | ||
| - | <StructureSection load='7ara' size='340' side='right'caption='[[7ara]]' scene=''> | + | <StructureSection load='7ara' size='340' side='right'caption='[[7ara]], [[Resolution|resolution]] 2.24Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ARA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ARA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7ara]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hrv-2 Hrv-2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ARA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ARA FirstGlance]. <br> |
| - | </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=7ara FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ara OCA], [https://pdbe.org/7ara PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ara RCSB], [https://www.ebi.ac.uk/pdbsum/7ara PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ara ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S7N:(phenylmethyl)+~{N}-[(2~{R})-3-methyl-1-[[(2~{S})-1-[[(3~{S})-1-methylsulfanyl-4-oxidanylidene-pentan-3-yl]amino]-1-oxidanylidene-propan-2-yl]amino]-1-oxidanylidene-butan-2-yl]carbamate'>S7N</scene>, <scene name='pdbligand=S7Q:(phenylmethyl)+~{N}-[(2~{S})-3-methyl-1-[[(2~{R})-1-[[(3~{R})-1-methylsulfanyl-4-oxidanylidene-pentan-3-yl]amino]-1-oxidanylidene-propan-2-yl]amino]-1-oxidanylidene-butan-2-yl]carbamate'>S7Q</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7ara FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ara OCA], [https://pdbe.org/7ara PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ara RCSB], [https://www.ebi.ac.uk/pdbsum/7ara PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ara ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/POLG_HRV2 POLG_HRV2]] Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with human VLDLR to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis. VP4 and VP1 subsequently undergo conformational changes leading to the formation of a pore in the endosomal membrane, thereby delivering the viral genome into the cytoplasm.<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> VP0 precursor is a component of immature procapsids (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> Protein 2A is a cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA transcription.<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Picornavirus family members cause disease in humans. Human rhinoviruses (RV), the main causative agents of the common cold, increase the severity of asthma and COPD; hence, effective agents against RVs are required. The 2A proteinase (2A(pro)), found in all enteroviruses, represents an attractive target; inactivating mutations in poliovirus 2A(pro) result in an extension of the VP1 protein preventing infectious virion assembly. Variations in sequence and substrate specificity on eIF4G isoforms between RV 2A(pro) of genetic groups A and B hinder 2A(pro) as drug targets. Here, we demonstrate that although RV-A2 and RV-B4 2A(pro) cleave the substrate GAB1 at different sites, the 2A(pro) from both groups cleave equally efficiently an artificial site containing P1 methionine. We determined the RV-A2 2A(pro) structure complexed with zVAM.fmk, containing P1 methionine. Analysis of this first 2A(pro)-inhibitor complex reveals a conserved hydrophobic P4 pocket among enteroviral 2A(pro) as a potential target for broad-spectrum anti-enteroviral inhibitors. | ||
| + | |||
| + | Defining substrate selection by rhinoviral 2A proteinase through its crystal structure with the inhibitor zVAM.fmk.,Deutschmann-Olek KM, Yue WW, Bezerra GA, Skern T Virology. 2021 Jul 21;562:128-141. doi: 10.1016/j.virol.2021.07.008. PMID:34315103<ref>PMID:34315103</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7ara" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Hrv-2]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Bezerra | + | [[Category: Bezerra, G A]] |
| - | [[Category: Deutschmann-Olek | + | [[Category: Deutschmann-Olek, K M]] |
| - | [[Category: Skern T]] | + | [[Category: Skern, T]] |
| - | [[Category: Yue | + | [[Category: Yue, W W]] |
| + | [[Category: Chymotrypsin-like cysteine protease]] | ||
| + | [[Category: Rhinoviral 2a protease]] | ||
| + | [[Category: Viral protein]] | ||
| + | [[Category: Zvam fmk]] | ||
Revision as of 10:31, 4 August 2021
Rhinovirus A2 2A protease in complex with zVAM.fmk
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