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==structure of hetero complex of non structural protein (NS) of hepatitis C virus (HCV) and synthetic peptidic compound== | |||
<StructureSection load='1dxw' size='340' side='right'caption='[[1dxw]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1dxw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_C Hepacivirus C]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DXW FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2ZF:N-(TERT-BUTOXYCARBONYL)-L-ALPHA-GLUTAMYL-N-[(1R)-1-(CARBOXYCARBONYL)-3,3-DIFLUOROPROPYL]-L-LEUCINAMIDE'>2ZF</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1dxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dxw OCA], [https://pdbe.org/1dxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dxw RCSB], [https://www.ebi.ac.uk/pdbsum/1dxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dxw ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8QW30_9HEPC Q8QW30_9HEPC] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
== | |||
Few structures of viral serine proteases, those encoded by the Sindbis and Semliki Forest viruses, hepatitis C virus (HCV) and cytomegalovirus, have been reported. In the life cycle of HCV a crucial role is played by a chymotrypsin-like serine protease encoded at the N-terminus of the viral NS3 protein, the solution structure of which we present here complexed with a covalently bound reversible inhibitor. Unexpectedly, the residue in the P2 position of the inhibitor induces an effective stabilization of the catalytic His-Asp hydrogen bond, by shielding that region of the protease from the solvent. This interaction appears crucial in the activation of the enzyme catalytic machinery and represents an unprecedented observation for this family of enzymes. Our data suggest that natural substrates of this serine protease could contribute to the enzyme activation by a similar induced-fit mechanism. The high degree of similarity at the His-Asp catalytic site region between HCV NS3 and other viral serine proteases suggests that this behaviour could be a more general feature for this category of viral enzymes. | Few structures of viral serine proteases, those encoded by the Sindbis and Semliki Forest viruses, hepatitis C virus (HCV) and cytomegalovirus, have been reported. In the life cycle of HCV a crucial role is played by a chymotrypsin-like serine protease encoded at the N-terminus of the viral NS3 protein, the solution structure of which we present here complexed with a covalently bound reversible inhibitor. Unexpectedly, the residue in the P2 position of the inhibitor induces an effective stabilization of the catalytic His-Asp hydrogen bond, by shielding that region of the protease from the solvent. This interaction appears crucial in the activation of the enzyme catalytic machinery and represents an unprecedented observation for this family of enzymes. Our data suggest that natural substrates of this serine protease could contribute to the enzyme activation by a similar induced-fit mechanism. The high degree of similarity at the His-Asp catalytic site region between HCV NS3 and other viral serine proteases suggests that this behaviour could be a more general feature for this category of viral enzymes. | ||
Inhibitor binding induces active site stabilization of the HCV NS3 protein serine protease domain.,Barbato G, Cicero DO, Cordier F, Narjes F, Gerlach B, Sambucini S, Grzesiek S, Matassa VG, De Francesco R, Bazzo R EMBO J. 2000 Mar 15;19(6):1195-206. PMID:10716920<ref>PMID:10716920</ref> | |||
Inhibitor binding induces active site stabilization of the HCV NS3 protein serine protease domain., Barbato G, Cicero DO, Cordier F, Narjes F, Gerlach B, Sambucini S, Grzesiek S, Matassa VG, De Francesco R, Bazzo R | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1dxw" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Hepacivirus C]] | |||
[[Category: Large Structures]] | |||
[[Category: Barbato G]] | |||
[[Category: Bazzo R]] | |||
[[Category: Cicero DO]] | |||
[[Category: Cordier F]] | |||
[[Category: Defrancesco R]] | |||
[[Category: Gerlach B]] | |||
[[Category: Grzesiek S]] | |||
[[Category: Matassa VG]] | |||
[[Category: Narjes F]] | |||
[[Category: Sambucini S]] | |||
Latest revision as of 13:37, 14 December 2022
structure of hetero complex of non structural protein (NS) of hepatitis C virus (HCV) and synthetic peptidic compoundstructure of hetero complex of non structural protein (NS) of hepatitis C virus (HCV) and synthetic peptidic compound
Structural highlights
FunctionPublication Abstract from PubMedFew structures of viral serine proteases, those encoded by the Sindbis and Semliki Forest viruses, hepatitis C virus (HCV) and cytomegalovirus, have been reported. In the life cycle of HCV a crucial role is played by a chymotrypsin-like serine protease encoded at the N-terminus of the viral NS3 protein, the solution structure of which we present here complexed with a covalently bound reversible inhibitor. Unexpectedly, the residue in the P2 position of the inhibitor induces an effective stabilization of the catalytic His-Asp hydrogen bond, by shielding that region of the protease from the solvent. This interaction appears crucial in the activation of the enzyme catalytic machinery and represents an unprecedented observation for this family of enzymes. Our data suggest that natural substrates of this serine protease could contribute to the enzyme activation by a similar induced-fit mechanism. The high degree of similarity at the His-Asp catalytic site region between HCV NS3 and other viral serine proteases suggests that this behaviour could be a more general feature for this category of viral enzymes. Inhibitor binding induces active site stabilization of the HCV NS3 protein serine protease domain.,Barbato G, Cicero DO, Cordier F, Narjes F, Gerlach B, Sambucini S, Grzesiek S, Matassa VG, De Francesco R, Bazzo R EMBO J. 2000 Mar 15;19(6):1195-206. PMID:10716920[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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