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| | <StructureSection load='1a5v' size='340' side='right'caption='[[1a5v]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='1a5v' size='340' side='right'caption='[[1a5v]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1a5v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rsvsr Rsvsr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A5V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1a5v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rous_sarcoma_virus_(strain_Schmidt-Ruppin) Rous sarcoma virus (strain Schmidt-Ruppin)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A5V FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=Y3:4-ACETYLAMINO-5-HYDROXYNAPHTHALENE-2,7-DISULFONIC+ACID'>Y3</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]] 1.9Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=Y3:4-ACETYLAMINO-5-HYDROXYNAPHTHALENE-2,7-DISULFONIC+ACID'>Y3</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=1a5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a5v OCA], [https://pdbe.org/1a5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a5v RCSB], [https://www.ebi.ac.uk/pdbsum/1a5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a5v 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=1a5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a5v OCA], [https://pdbe.org/1a5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a5v RCSB], [https://www.ebi.ac.uk/pdbsum/1a5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a5v ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/POL_RSVP POL_RSVP]] Capsid protein p27 forms the spherical core of the virus that encapsulates the genomic RNA-nucleocapsid complex (By similarity). The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell (By similarity).
| + | [https://www.uniprot.org/uniprot/POL_RSVSB POL_RSVSB] Capsid protein p27: Self-associates to form the irregular polyhedron core composed of hexamers and pentamers, that encapsulates the genomic RNA-nucleocapsid complex. Assembles as a tube in vitro. Binds to inositol hexakisphosphate (IP6), which allows the assembly of the polyhedral capsid.[UniProtKB:P03322] Plays a role in the oligomerization of the Gag polyprotein and in the stabilization of the immature particle. Essential layering element during tube assembly. Allows the cooperative binging of Gag to the host plasma membrane.[UniProtKB:P03322] Binds strongly to viral nucleic acids and promotes their packaging (By similarity). Plays a role in the maturation-stabilization of the viral dimeric RNA via highly structured zinc-binding motifs (By similarity).[UniProtKB:P03322][UniProtKB:P0C776] The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell.[PROSITE-ProRule:PRU00275] Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions (PubMed:9218451). This recombination event is an essential step in the viral replication cycle. Has a strong preference for using the 3'-OH at the viral DNA end as a nucleophile.[UniProtKB:P03354]<ref>PMID:9218451</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RNA-directed DNA polymerase]]
| + | [[Category: Alexandratos J]] |
| - | [[Category: Rsvsr]]
| + | [[Category: Lubkowski J]] |
| - | [[Category: Alexandratos, J]] | + | [[Category: Wlodawer A]] |
| - | [[Category: Lubkowski, J]] | + | [[Category: Yang F]] |
| - | [[Category: Wlodawer, A]] | + | |
| - | [[Category: Yang, F]] | + | |
| - | [[Category: Endonuclease]]
| + | |
| - | [[Category: Hiv-1 integrase inhibitor]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
POL_RSVSB Capsid protein p27: Self-associates to form the irregular polyhedron core composed of hexamers and pentamers, that encapsulates the genomic RNA-nucleocapsid complex. Assembles as a tube in vitro. Binds to inositol hexakisphosphate (IP6), which allows the assembly of the polyhedral capsid.[UniProtKB:P03322] Plays a role in the oligomerization of the Gag polyprotein and in the stabilization of the immature particle. Essential layering element during tube assembly. Allows the cooperative binging of Gag to the host plasma membrane.[UniProtKB:P03322] Binds strongly to viral nucleic acids and promotes their packaging (By similarity). Plays a role in the maturation-stabilization of the viral dimeric RNA via highly structured zinc-binding motifs (By similarity).[UniProtKB:P03322][UniProtKB:P0C776] The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell.[PROSITE-ProRule:PRU00275] Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions (PubMed:9218451). This recombination event is an essential step in the viral replication cycle. Has a strong preference for using the 3'-OH at the viral DNA end as a nucleophile.[UniProtKB:P03354][1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The x-ray structures of an inhibitor complex of the catalytic core domain of avian sarcoma virus integrase (ASV IN) were solved at 1.9- to 2.0-A resolution at two pH values, with and without Mn2+ cations. This inhibitor (Y-3), originally identified in a screen for inhibitors of the catalytic activity of HIV type 1 integrase (HIV-1 IN), was found in the present study to be active against ASV IN as well as HIV-1 IN. The Y-3 molecule is located in close proximity to the enzyme active site, interacts with the flexible loop, alters loop conformation, and affects the conformations of active site residues. As crystallized, a Y-3 molecule stacks against its symmetry-related mate. Preincubation of IN with metal cations does not prevent inhibition, and Y-3 binding does not prevent binding of divalent cations to IN. Three compounds chemically related to Y-3 also were investigated, but no binding was observed in the crystals. Our results identify the structural elements of the inhibitor that likely determine its binding properties.
Structure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor.,Lubkowski J, Yang F, Alexandratos J, Wlodawer A, Zhao H, Burke TR Jr, Neamati N, Pommier Y, Merkel G, Skalka AM Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4831-6. PMID:9560188[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bujacz G, Alexandratos J, Wlodawer A, Merkel G, Andrake M, Katz RA, Skalka AM. Binding of different divalent cations to the active site of avian sarcoma virus integrase and their effects on enzymatic activity. J Biol Chem. 1997 Jul 18;272(29):18161-8. PMID:9218451
- ↑ Lubkowski J, Yang F, Alexandratos J, Wlodawer A, Zhao H, Burke TR Jr, Neamati N, Pommier Y, Merkel G, Skalka AM. Structure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4831-6. PMID:9560188
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