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| == Function == | | == Function == |
| [https://www.uniprot.org/uniprot/A8DG50_9HEPC A8DG50_9HEPC] | | [https://www.uniprot.org/uniprot/A8DG50_9HEPC A8DG50_9HEPC] |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Hepatitis C NS3/4A protease is a prime therapeutic target responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A and 5A5B, and two host-cell adapter proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host-cell cleavage sites are determined and compared to the crystal structures of viral substrates. Two distinct protease conformations are observed and correlate with substrate specificity: (1) 3-4A, 4A4B, 5A5B and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease and (2) TRIF and 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes. These findings provide mechanistic insights into NS3/4A substrate recognition, which may assist in a more rational approach to inhibitor design in the face of the rapid acquisition of resistance.
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| Molecular mechanisms of viral and host-cell substrate recognition by HCV NS3/4A protease.,Romano KP, Laine JM, Deveau LM, Cao H, Massi F, Schiffer CA J Virol. 2011 Apr 20. PMID:21507982<ref>PMID:21507982</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 3rc6" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Virus protease 3D structures|Virus protease 3D structures]] | | *[[Virus protease 3D structures|Virus protease 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |