View source for 1nju


==Complex structure of HCMV Protease and a peptidomimetic inhibitor==
<StructureSection load='1nju' size='340' side='right'caption='[[1nju]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1nju]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_betaherpesvirus_5 Human betaherpesvirus 5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NJU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NJU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0FP:N-(6-AMINOHEXANOYL)-3-METHYL-L-VALYL-3-METHYL-L-VALYL-N~1~-[(2S,3S)-3-HYDROXY-4-OXO-4-{[(1R)-1-PHENYLPROPYL]AMINO}BUTAN-2-YL]-N~4~,N~4~-DIMETHYL-L-ASPARTAMIDE'>0FP</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=1nju FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nju OCA], [https://pdbe.org/1nju PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nju RCSB], [https://www.ebi.ac.uk/pdbsum/1nju PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nju ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SCAF_HCMVA SCAF_HCMVA] Capsid scaffolding protein acts as a scaffold protein by binding major capsid protein UL86 in the cytoplasm, inducing the nuclear localization of both proteins. Multimerizes in the nucleus such as protein UL86 forms the icosahedral T=16 capsid. Autocatalytic cleavage releases the assembly protein, and subsequently abolishes interaction with major capsid protein UL86. Cleavages products are evicted from the capsid before or during DNA packaging (By similarity).  Assemblin is a protease essential for virion assembly in the nucleus. Catalyzes the cleavage of the assembly protein after complete capsid formation. Assemblin and cleavages products are evicted from the capsid before or during DNA packaging (By similarity).  Assembly protein plays a major role in capsid assembly. Acts as a scaffold protein by binding major capsid protein UL86. Multimerizes in the nucleus such as protein UL86 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 (By similarity).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nj/1nju_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1nju ConSurf].
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== Publication Abstract from PubMed ==
Herpesvirus protease is required for the life cycle of the virus and is an attractive target for the design and development of new anti-herpes agents. The protease belongs to a new class of serine proteases, with a novel backbone fold and a unique Ser-His-His catalytic triad. Here we report the crystal structures of human cytomegalovirus protease in complex with two peptidomimetic inhibitors. The structures reveal a new hydrogen-bonding interaction between the main chain carbonyl of the P(5) residue and the main chain amide of amino acid 137 of the protease, which is important for the binding affinity of the inhibitor. Conformational flexibility was observed in the S(3) pocket of the enzyme, and this is supported by our characterization of several mutants in this pocket. One of the structures is at 2.5 A resolution, allowing us for the first time to locate ordered solvent molecules in the inhibitor complex. The presence of two solvent molecules in the active site may have implications for the design of new inhibitors against this enzyme. Favorable and stereospecific interactions have been established in the S(1)' pocket for one of these inhibitors.

Structural and biochemical studies of inhibitor binding to human cytomegalovirus protease.,Khayat R, Batra R, Qian C, Halmos T, Bailey M, Tong L Biochemistry. 2003 Feb 4;42(4):885-91. PMID:12549906<ref>PMID:12549906</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Virus protease 3D structures|Virus protease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human betaherpesvirus 5]]
[[Category: Large Structures]]
[[Category: Bailey M]]
[[Category: Batra R]]
[[Category: Halmos T]]
[[Category: Khayat R]]
[[Category: Qian C]]
[[Category: Tong L]]