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[[Image:1fl1.jpg|left|200px]]<br /><applet load="1fl1" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1fl1, resolution 2.20&Aring;" />
'''KSHV PROTEASE'''<br />


==Overview==
==KSHV PROTEASE==
The structure of Kaposi's sarcoma-associated herpesvirus protease (KSHV Pr), at 2.2 A resolution, reveals the active-site geometry and defines multiple possible target sites for drug design against a human cancer-producing virus. The catalytic triad of KSHV Pr, (Ser114, His46, and His157) and transition-state stabilization site are arranged as in other structurally characterized herpesviral proteases. The distal histidine-histidine hydrogen bond is solvent accessible, unlike the situation in other classes of serine proteases. As in all herpesviral proteases, the enzyme is active only as a weakly associated dimer (K(d) approximately 2 microM), and inactive as a monomer. Therefore, both the active site and dimer interface are potential targets for antiviral drug design. The dimer interface in KSHV Pr is compared with the interface of other herpesviral proteases. Two conserved arginines (Arg209), one from each monomer, are buried within the same region of the dimer interface. We propose that this conserved arginine may provide a destabilizing element contributing to the tuned micromolar dissociation of herpesviral protease dimers.
<StructureSection load='1fl1' size='340' side='right'caption='[[1fl1]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[1fl1]] is a 2 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=1FL1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FL1 FirstGlance]. <br>
1FL1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_herpesvirus_4 Human herpesvirus 4] with <scene name='pdbligand=K:'>K</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FL1 OCA].  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1fl1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fl1 OCA], [https://pdbe.org/1fl1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fl1 RCSB], [https://www.ebi.ac.uk/pdbsum/1fl1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fl1 ProSAT]</span></td></tr>
Functional consequences of the Kaposi's sarcoma-associated herpesvirus protease structure: regulation of activity and dimerization by conserved structural elements., Reiling KK, Pray TR, Craik CS, Stroud RM, Biochemistry. 2000 Oct 24;39(42):12796-803. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11041844 11041844]
</table>
[[Category: Human herpesvirus 4]]
== Function ==
[[Category: Single protein]]
[https://www.uniprot.org/uniprot/O36607_HHV8 O36607_HHV8]  
[[Category: Craik, C S.]]
== Evolutionary Conservation ==
[[Category: Pray, T R.]]
[[Image:Consurf_key_small.gif|200px|right]]
[[Category: Reiling, K K.]]
Check<jmol>
[[Category: Stroud, R M.]]
  <jmolCheckbox>
[[Category: K]]
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fl/1fl1_consurf.spt"</scriptWhenChecked>
[[Category: antiviral drug design]]
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
[[Category: assemblin]]
    <text>to colour the structure by Evolutionary Conservation</text>
[[Category: capsid maturation]]
  </jmolCheckbox>
[[Category: endopeptidase]]
</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=1fl1 ConSurf].
[[Category: serine protease]]
<div style="clear:both"></div>
 
__TOC__
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:39:46 2008''
</StructureSection>
[[Category: Human gammaherpesvirus 8]]
[[Category: Large Structures]]
[[Category: Craik CS]]
[[Category: Pray TR]]
[[Category: Reiling KK]]
[[Category: Stroud RM]]

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