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7tcz

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Revision as of 17:03, 18 October 2023

Human cytomegalovirus protease mutant (C84A, C87A, C138A, C202A) in complex with inhibitor

Structural highlights

7tcz is a 1 chain structure with sequence from Human betaherpesvirus 5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.67Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).

Publication Abstract from PubMed

Viruses are responsible for some of the most deadly human diseases, yet available vaccines and antivirals address only a fraction of the potential viral human pathogens. Here, we provide a methodology for managing human herpesvirus (HHV) infection by covalently inactivating the HHV maturational protease via a conserved, non-catalytic cysteine (C161). Using human cytomegalovirus protease (HCMV Pr) as a model, we screened a library of disulfides to identify molecules that tether to C161 and inhibit proteolysis, then elaborated hits into irreversible HCMV Pr inhibitors that exhibit broad-spectrum inhibition of other HHV Pr homologs. We further developed an optimized tool compound targeted toward HCMV Pr and used an integrative structural biology and biochemical approach to demonstrate inhibitor stabilization of HCMV Pr homodimerization, exploiting a conformational equilibrium to block proteolysis. Irreversible HCMV Pr inhibition disrupts HCMV infectivity in cells, providing proof of principle for targeting proteolysis via a non-catalytic cysteine to manage viral infection.

Inhibiting a dynamic viral protease by targeting a non-catalytic cysteine.,Hulce KR, Jaishankar P, Lee GM, Bohn MF, Connelly EJ, Wucherer K, Ongpipattanakul C, Volk RF, Chuo SW, Arkin MR, Renslo AR, Craik CS Cell Chem Biol. 2022 Mar 30. pii: S2451-9456(22)00124-6. doi:, 10.1016/j.chembiol.2022.03.007. PMID:35364007^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hulce KR, Jaishankar P, Lee GM, Bohn MF, Connelly EJ, Wucherer K, Ongpipattanakul C, Volk RF, Chuo SW, Arkin MR, Renslo AR, Craik CS. Inhibiting a dynamic viral protease by targeting a non-catalytic cysteine. Cell Chem Biol. 2022 Mar 30. pii: S2451-9456(22)00124-6. doi:, 10.1016/j.chembiol.2022.03.007. PMID:35364007 doi:http://dx.doi.org/10.1016/j.chembiol.2022.03.007

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7tcz"

@@ Line 3: / Line 3: @@
 <StructureSection load='7tcz' size='340' side='right'caption='[[7tcz]], [[Resolution|resolution]] 2.67&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7tcz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TCZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TCZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7tcz]] is a 1 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=7TCZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TCZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GIT:[1-(2-oxopropyl)-4-phenyl-1H-1,2,3-triazol-5-yl]methyl+benzylcarbamate'>GIT</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]] 2.67&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Assemblin Assemblin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.97 3.4.21.97] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GIT:[1-(2-oxopropyl)-4-phenyl-1H-1,2,3-triazol-5-yl]methyl+benzylcarbamate'>GIT</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=7tcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tcz OCA], [https://pdbe.org/7tcz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tcz RCSB], [https://www.ebi.ac.uk/pdbsum/7tcz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tcz ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/A0A126N917_HCMV A0A126N917_HCMV]] Assemblin: 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]  Assembly protein: 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]  Capsid scaffolding protein: 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]
+[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).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Assemblin]]
+[[Category: Human betaherpesvirus 5]]
 [[Category: Large Structures]]
-[[Category: Bohn, M]]
+[[Category: Bohn M]]
-[[Category: Craik, C S]]
+[[Category: Craik CS]]
-[[Category: Hulce, K R]]
+[[Category: Hulce KR]]
-[[Category: Jaishankar, P]]
+[[Category: Jaishankar P]]
-[[Category: Ongpipattanakul, C]]
+[[Category: Ongpipattanakul C]]
-[[Category: Renslo, A R]]
+[[Category: Renslo AR]]
-[[Category: Hyrdrolase-hydrolase inhibitor complex]]
-[[Category: Protease]]
-[[Category: Viral protein]]

7tcz

From Proteopedia

Revision as of 17:03, 18 October 2023

Human cytomegalovirus protease mutant (C84A, C87A, C138A, C202A) in complex with inhibitor

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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