2pbk

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[[Image:2pbk.png|left|200px]]
 
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{{STRUCTURE_2pbk| PDB=2pbk | SCENE= }}
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==Crystal structure of KSHV protease in complex with hexapeptide phosphonate inhibitor==
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<StructureSection load='2pbk' size='340' side='right'caption='[[2pbk]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2pbk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_gammaherpesvirus_8 Human gammaherpesvirus 8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PBK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PBK FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.73&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GG7:[(1R)-1-AMINOETHYL]PHOSPHONIC+ACID'>GG7</scene>, <scene name='pdbligand=TBG:3-METHYL-L-VALINE'>TBG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pbk OCA], [https://pdbe.org/2pbk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pbk RCSB], [https://www.ebi.ac.uk/pdbsum/2pbk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pbk ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SCAF_HHV8P SCAF_HHV8P] 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]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pb/2pbk_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2pbk ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The herpesvirus proteases are an example in which allosteric regulation of an enzyme activity is achieved through the formation of quaternary structure. Here, we report a 1.7 A resolution structure of Kaposi's sarcoma-associated herpesvirus protease in complex with a hexapeptide transition state analogue that stabilizes the dimeric state of the enzyme. Extended substrate binding sites are induced upon peptide binding. In particular, 104 A2 of surface are buried in the newly formed S4 pocket when tyrosine binds at this site. The peptide inhibitor also induces a rearrangement of residues that stabilizes the oxyanion hole and the dimer interface. Concomitant with the structural changes, an increase in catalytic efficiency of the enzyme results upon extended substrate binding. A nearly 20-fold increase in kcat/KM results upon extending the peptide substrate from a tetrapeptide to a hexapeptide exclusively due to a KM effect. This suggests that the mechanism by which herpesvirus proteases achieve their high specificity is by using extended substrates to modulate both the structure and activity of the enzyme.
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===Crystal structure of KSHV protease in complex with hexapeptide phosphonate inhibitor===
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Substrate modulation of enzyme activity in the herpesvirus protease family.,Lazic A, Goetz DH, Nomura AM, Marnett AB, Craik CS J Mol Biol. 2007 Nov 2;373(4):913-23. Epub 2007 Aug 16. PMID:17870089<ref>PMID:17870089</ref>
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{{ABSTRACT_PUBMED_17870089}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 2pbk" style="background-color:#fffaf0;"></div>
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[[2pbk]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_herpesvirus_8 Human herpesvirus 8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PBK OCA].
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== References ==
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<references/>
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==Reference==
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__TOC__
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<ref group="xtra">PMID:017870089</ref><references group="xtra"/>
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</StructureSection>
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[[Category: Human herpesvirus 8]]
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[[Category: Human gammaherpesvirus 8]]
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[[Category: Goetz, D H.]]
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[[Category: Large Structures]]
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[[Category: Lazic, A.]]
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[[Category: Goetz DH]]
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[[Category: Herpesvirus protease]]
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[[Category: Lazic A]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Kshv]]
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[[Category: Kshv protease]]
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[[Category: Viral protease]]
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[[Category: Viral protein]]
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Current revision

Crystal structure of KSHV protease in complex with hexapeptide phosphonate inhibitor

PDB ID 2pbk

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