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5gpi
From Proteopedia
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(New page: '''Unreleased structure''' The entry 5gpi is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structures of Unlinked NS2B-NS3 Protease from Zika Virus and Its Complex with a Reverse Peptide Inhibitor== | |
| + | <StructureSection load='5gpi' size='340' side='right'caption='[[5gpi]], [[Resolution|resolution]] 1.58Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5gpi]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Zika_virus Zika virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GPI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GPI 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]] 1.578Å</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=5gpi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gpi OCA], [https://pdbe.org/5gpi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gpi RCSB], [https://www.ebi.ac.uk/pdbsum/5gpi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gpi ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/POLG_ZIKV POLG_ZIKV] Protein C: Encapsulates the genomic RNA.[UniProtKB:P17763] prM: Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated.[UniProtKB:P17763] Envelope protein E: Binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes.[UniProtKB:P17763] Non-structural protein 1: Involved in virus replication and regulation of the innate immune response.[UniProtKB:P17763] Non-structural protein 2A: May be involved viral RNA replication and capsid assembly.[UniProtKB:P09732] Non-structural protein 4A: Induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the helicase region of Serine protease NS3 chain.[UniProtKB:P17763] Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[UniProtKB:P17763] Non-structural protein 4B: Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway.[UniProtKB:P17763] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Zika virus (ZIKV) has rapidly emerged as a global public health concern. Viral NS2B-NS3 protease processes viral polyprotein and is essential for the virus replication, making it an attractive antiviral drug target. We report crystal structures at 1.58-angstrom resolution of the unlinked NS2B-NS3 protease from ZIKV as free enzyme and bound to a peptide reversely oriented at the active site. The unlinked NS2B-NS3 protease adopts a closed conformation in which NS2B engages NS3 to form an empty substrate-binding site. A second protease in the same crystal binds to the residues K14K15G16E17 from the neighboring NS3 in reverse orientation, resisting proteolysis. These features of ZIKV NS2B-NS3 protease may accelerate the discovery of structure-based antiviral drugs against ZIKV and related pathogenic flaviviruses. | ||
| - | + | Crystal structure of unlinked NS2B-NS3 protease from Zika virus.,Zhang Z, Li Y, Loh YR, Phoo WW, Hung AW, Kang C, Luo D Science. 2016 Dec 23;354(6319):1597-1600. doi: 10.1126/science.aai9309. Epub 2016, Dec 8. PMID:27940580<ref>PMID:27940580</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5gpi" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Virus protease 3D structures|Virus protease 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Zika virus]] | ||
| + | [[Category: Phoo WW]] | ||
| + | [[Category: Zhang ZZ]] | ||
Current revision
Crystal Structures of Unlinked NS2B-NS3 Protease from Zika Virus and Its Complex with a Reverse Peptide Inhibitor
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