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| | <StructureSection load='2xya' size='340' side='right'caption='[[2xya]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='2xya' size='340' side='right'caption='[[2xya]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2xya]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_rhinovirus Human rhinovirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XYA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XYA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2xya]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_rhinovirus_sp. Human rhinovirus sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XYA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XYA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7L4:2-PHENYLQUINOLIN-4-OL'>7L4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1a3r|1a3r]], [[1cqq|1cqq]], [[2hrv|2hrv]], [[1v9u|1v9u]], [[1fpn|1fpn]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7L4:2-PHENYLQUINOLIN-4-OL'>7L4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </span></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=2xya FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xya OCA], [https://pdbe.org/2xya PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xya RCSB], [https://www.ebi.ac.uk/pdbsum/2xya PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xya ProSAT]</span></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=2xya FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xya OCA], [https://pdbe.org/2xya PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xya RCSB], [https://www.ebi.ac.uk/pdbsum/2xya PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xya ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human rhinovirus]] | + | [[Category: Human rhinovirus sp]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Picornain 3C]]
| + | [[Category: Edfeldt F]] |
| - | [[Category: Edfeldt, F]] | + | [[Category: Edman K]] |
| - | [[Category: Edman, K]] | + | [[Category: Johansson C]] |
| - | [[Category: Johansson, C]] | + | [[Category: Petersen J]] |
| - | [[Category: Petersen, J]] | + | |
| - | [[Category: Cysteine protease]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
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.[1] [2] VP0 precursor is a component of immature procapsids (By similarity).[3] [4] 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.[5] [6] Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).[7] [8] Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).[9] [10] Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity).[11] [12] 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).[13] [14] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[15] [16]
Publication Abstract from PubMed
The first known non-covalent inhibitors of rhinovirus 3C protease (3CP) have been identified through fragment based screening and hit identification activities.
Non-covalent inhibitors of rhinovirus 3C protease.,Baxter A, Chambers M, Edfeldt F, Edman K, Freeman A, Johansson C, King S, Morley A, Petersen J, Rawlins P, Spadola L, Thong B, Van de Poel H, Williams N Bioorg Med Chem Lett. 2011 Jan 15;21(2):777-80. Epub 2010 Nov 26. PMID:21183345[17]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Baxter A, Chambers M, Edfeldt F, Edman K, Freeman A, Johansson C, King S, Morley A, Petersen J, Rawlins P, Spadola L, Thong B, Van de Poel H, Williams N. Non-covalent inhibitors of rhinovirus 3C protease. Bioorg Med Chem Lett. 2011 Jan 15;21(2):777-80. Epub 2010 Nov 26. PMID:21183345 doi:10.1016/j.bmcl.2010.11.110
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