8i71

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'''Unreleased structure'''
 
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The entry 8i71 is ON HOLD until Paper Publication
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==Hepatitis B virus core protein Y132A mutant in complex with Linvencorvir (RG7907), a Hepatitis B Virus (HBV) Core Protein Allosteric Modulator (CpAM)==
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<StructureSection load='8i71' size='340' side='right'caption='[[8i71]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8i71]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatitis_B_virus_subtype_adyw Hepatitis B virus subtype adyw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8I71 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8I71 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=OTI:3-[(8~{a}~{S})-7-[[5-ethoxycarbonyl-4-(3-fluoranyl-2-methyl-phenyl)-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidin-6-yl]methyl]-3-oxidanylidene-5,6,8,8~{a}-tetrahydro-1~{H}-imidazo[1,5-a]pyrazin-2-yl]-2,2-dimethyl-propanoic+acid'>OTI</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8i71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8i71 OCA], [https://pdbe.org/8i71 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8i71 RCSB], [https://www.ebi.ac.uk/pdbsum/8i71 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8i71 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CAPSD_HBVD1 CAPSD_HBVD1] Self assembles to form an icosahedral capsid. Most capsid appear to be large particles with a icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller T=3 particles consisting of 180 capsid proteins. Entering capsid are transported along microtubules to the nucleus. Phosphorylation of the capsid is thought to induce exposure of nuclear localization signal in the C-terminal portion of the capsid protein that allows binding to the nuclear pore complex via the importin (karyopherin-) alpha and beta. Capsids are imported in intact form through the nuclear pore into the nuclear basket, where it probably binds NUP153. Only capsids that contain the mature viral genome can release the viral DNA and capsid protein into the nucleoplasm. Immature capsids get stucked in the basket. Capsids encapsulate the pre-genomic RNA and the P protein. Pre-genomic RNA is reverse transcribed into DNA while the capsid is still in the cytoplasm. The capsid can then either be directed to the nucleus, providing more genome for transcription, or bud through the endoplasmic reticulum to provide new virions (By similarity).<ref>PMID:7711014</ref> Encapsidates hepatitis delta genome (By similarity).<ref>PMID:7711014</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Described herein is the first-time disclosure of Linvencorvir (RG7907), a clinical compound and a hepatitis B virus (HBV) core protein allosteric modulator, for the treatment of chronic HBV infection. Built upon the core structure of hetero aryl dihydropyrimidine, RG7907 was rationally designed by combining all the drug-like features of low CYP3A4 induction, potent anti-HBV activity, high metabolic stability, low hERG liability, and favorable animal pharmacokinetic (PK) profiles. In particular, the chemistry strategy to mitigate CYP3A4 induction through introducing a large, rigid, and polar substituent at the position that has less interaction with the therapeutic biological target (HBV core proteins herein) is of general interest to the medicinal chemistry community. RG7907 demonstrated favorable animal PK, pharmacodynamics, and safety profiles with sufficient safety margins supporting its clinical development in healthy volunteers and HBV-infected patients.
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Authors: Zhou, Z., Xu, Z.H.
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Discovery of Linvencorvir (RG7907), a Hepatitis B Virus Core Protein Allosteric Modulator, for the Treatment of Chronic HBV Infection.,Zhang W, Guo L, Liu H, Wu G, Shi H, Zhou M, Zhang Z, Kou B, Hu T, Zhou Z, Xu Z, Zhou X, Zhou Y, Tian X, Yang G, Young JAT, Qiu H, Ottaviani G, Xie J, Mayweg AV, Shen HC, Zhu W J Med Chem. 2023 Mar 10. doi: 10.1021/acs.jmedchem.3c00173. PMID:36896968<ref>PMID:36896968</ref>
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Description: Hepatitis B virus core protein Y132A mutant in complex with Linvencorvir (RG7907), a Hepatitis B Virus (HBV) Core Protein Allosteric Modulator (CpAM)
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Zhou, Z]]
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<div class="pdbe-citations 8i71" style="background-color:#fffaf0;"></div>
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[[Category: Xu, Z.H]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Hepatitis B virus subtype adyw]]
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[[Category: Large Structures]]
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[[Category: Xu ZH]]
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[[Category: Zhou Z]]

Revision as of 07:29, 22 March 2023

Hepatitis B virus core protein Y132A mutant in complex with Linvencorvir (RG7907), a Hepatitis B Virus (HBV) Core Protein Allosteric Modulator (CpAM)

PDB ID 8i71

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