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| | ==Monomeric pseudorabies virus protease pUL26N at 2.1 A resolution== | | ==Monomeric pseudorabies virus protease pUL26N at 2.1 A resolution== |
| - | <StructureSection load='4v0t' size='340' side='right' caption='[[4v0t]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='4v0t' size='340' side='right'caption='[[4v0t]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4v0t]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4V0T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4V0T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4v0t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Suid_alphaherpesvirus_1 Suid alphaherpesvirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4V0T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4V0T FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cx8|4cx8]], [[4v07|4v07]], [[4v08|4v08]]</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]] 2.05Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Assemblin Assemblin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.97 3.4.21.97] </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=4v0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v0t OCA], [https://pdbe.org/4v0t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4v0t RCSB], [https://www.ebi.ac.uk/pdbsum/4v0t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4v0t ProSAT]</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=4v0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v0t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4v0t RCSB], [http://www.ebi.ac.uk/pdbsum/4v0t PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SCAF_SUHVK SCAF_SUHVK] Acts as a scaffold protein by binding major capsid protein in the cytoplasm, inducing the nuclear localization of both proteins. Multimerizes in the nucleus such as major capsid protein forms the icosahedral T=16 capsid. Autocatalytic cleavage releases the assembly protein, and subsequently abolishes interaction with major capsid protein. Cleavages products are evicted from the capsid before or during DNA packaging.[HAMAP-Rule:MF_04008] Protease that plays an essential role in virion assembly within the nucleus. Catalyzes the cleavage of the assembly protein after formation of the spherical procapsid. By that cleavage, the capsid matures and gains its icosahedral shape. The cleavage sites seem to include -Ala-Ser-, -Ala-Ala-, as well as Ala-Thr bonds. Assemblin and cleavages products are evicted from the capsid before or during DNA packaging.[HAMAP-Rule:MF_04008] Plays a major role in capsid assembly. Acts as a scaffold protein by binding major capsid protein. Multimerizes in the nucleus such as major capsid protein forms the icosahedral T=16 capsid. Cleaved by assemblin after capsid completion. The cleavages products are evicted from the capsid before or during DNA packaging.[HAMAP-Rule:MF_04008] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4v0t" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Assemblin]] | + | [[Category: Large Structures]] |
| - | [[Category: Hinrichs, W]] | + | [[Category: Suid alphaherpesvirus 1]] |
| - | [[Category: Palm, G J]] | + | [[Category: Hinrichs W]] |
| - | [[Category: Werten, S]] | + | [[Category: Palm GJ]] |
| - | [[Category: Zuehlsdorf, M]] | + | [[Category: Werten S]] |
| - | [[Category: Herpes]]
| + | [[Category: Zuehlsdorf M]] |
| - | [[Category: Herpes virus]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Prv]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| - | [[Category: Suid]]
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| Structural highlights
Function
SCAF_SUHVK Acts as a scaffold protein by binding major capsid protein in the cytoplasm, inducing the nuclear localization of both proteins. Multimerizes in the nucleus such as major capsid protein forms the icosahedral T=16 capsid. Autocatalytic cleavage releases the assembly protein, and subsequently abolishes interaction with major capsid protein. Cleavages products are evicted from the capsid before or during DNA packaging.[HAMAP-Rule:MF_04008] Protease that plays an essential role in virion assembly within the nucleus. Catalyzes the cleavage of the assembly protein after formation of the spherical procapsid. By that cleavage, the capsid matures and gains its icosahedral shape. The cleavage sites seem to include -Ala-Ser-, -Ala-Ala-, as well as Ala-Thr bonds. Assemblin and cleavages products are evicted from the capsid before or during DNA packaging.[HAMAP-Rule:MF_04008] Plays a major role in capsid assembly. Acts as a scaffold protein by binding major capsid protein. Multimerizes in the nucleus such as major capsid protein forms the icosahedral T=16 capsid. Cleaved by assemblin after capsid completion. The cleavages products are evicted from the capsid before or during DNA packaging.[HAMAP-Rule:MF_04008]
Publication Abstract from PubMed
Herpesviruses encode a characteristic serine protease with a unique fold and an active site that comprises the unusual triad Ser-His-His. The protease is essential for viral replication and as such constitutes a promising drug target. In solution, a dynamic equilibrium exists between an inactive monomeric and an active dimeric form of the enzyme, which is believed to play a key regulatory role in the orchestration of proteolysis and capsid assembly. Currently available crystal structures of herpesvirus proteases correspond either to the dimeric state or to complexes with peptide mimetics that alter the dimerization interface. In contrast, the structure of the native monomeric state has remained elusive. Here, we present the three-dimensional structures of native monomeric, active dimeric, and diisopropyl fluorophosphate-inhibited dimeric protease derived from pseudorabies virus, an alphaherpesvirus of swine. These structures, solved by X-ray crystallography to respective resolutions of 2.05, 2.10 and 2.03 A, allow a direct comparison of the main conformational states of the protease. In the dimeric form, a functional oxyanion hole is formed by a loop of 10 amino-acid residues encompassing two consecutive arginine residues (Arg136 and Arg137); both are strictly conserved throughout the herpesviruses. In the monomeric form, the top of the loop is shifted by approximately 11 A, resulting in a complete disruption of the oxyanion hole and loss of activity. The dimerization-induced allosteric changes described here form the physical basis for the concentration-dependent activation of the protease, which is essential for proper virus replication. Small-angle X-ray scattering experiments confirmed a concentration-dependent equilibrium of monomeric and dimeric protease in solution.
Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease.,Zuhlsdorf M, Werten S, Klupp BG, Palm GJ, Mettenleiter TC, Hinrichs W PLoS Pathog. 2015 Jul 10;11(7):e1005045. doi: 10.1371/journal.ppat.1005045., eCollection 2015 Jul. PMID:26161660[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zuhlsdorf M, Werten S, Klupp BG, Palm GJ, Mettenleiter TC, Hinrichs W. Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease. PLoS Pathog. 2015 Jul 10;11(7):e1005045. doi: 10.1371/journal.ppat.1005045., eCollection 2015 Jul. PMID:26161660 doi:http://dx.doi.org/10.1371/journal.ppat.1005045
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