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| | ==CRYSTAL STRUCTURE OF THE HUMAN HEPATITIS B VIRUS T = 4 CAPSID, ADYW STRAIN, in COMPLEX WITH THE PHENYLPROPENAMIDE ASSEMBLY ACCELERATOR AT-130== | | ==CRYSTAL STRUCTURE OF THE HUMAN HEPATITIS B VIRUS T = 4 CAPSID, ADYW STRAIN, in COMPLEX WITH THE PHENYLPROPENAMIDE ASSEMBLY ACCELERATOR AT-130== |
| - | <StructureSection load='4g93' size='340' side='right' caption='[[4g93]], [[Resolution|resolution]] 4.20Å' scene=''> | + | <StructureSection load='4g93' size='340' side='right'caption='[[4g93]], [[Resolution|resolution]] 4.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4g93]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hbv-d Hbv-d]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G93 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4g93]] is a 4 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=4G93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G93 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0YP:N-[(1E)-1-BROMO-1-(2-METHOXYPHENYL)-3-OXO-3-(PIPERIDIN-1-YL)PROP-1-EN-2-YL]-4-NITROBENZAMIDE'>0YP</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0YP:N-[(1E)-1-BROMO-1-(2-METHOXYPHENYL)-3-OXO-3-(PIPERIDIN-1-YL)PROP-1-EN-2-YL]-4-NITROBENZAMIDE'>0YP</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2g33|2g33]], [[2g34|2g34]]</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=4g93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g93 OCA], [https://pdbe.org/4g93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g93 RCSB], [https://www.ebi.ac.uk/pdbsum/4g93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g93 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10419 HBV-D])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4g93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g93 OCA], [http://pdbe.org/4g93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4g93 RCSB], [http://www.ebi.ac.uk/pdbsum/4g93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4g93 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hbv-d]] | + | [[Category: Hepatitis B virus subtype adyw]] |
| - | [[Category: Katen, S P]] | + | [[Category: Large Structures]] |
| - | [[Category: Zlotnick, A]] | + | [[Category: Katen SP]] |
| - | [[Category: Assembly accelerator]] | + | [[Category: Zlotnick A]] |
| - | [[Category: Assembly effector]]
| + | |
| - | [[Category: Capsid]]
| + | |
| - | [[Category: Hepadnavirus]]
| + | |
| - | [[Category: Icosahedral]]
| + | |
| - | [[Category: Kinetic effector]]
| + | |
| - | [[Category: Phenylpropenamide]]
| + | |
| - | [[Category: Virus]]
| + | |
| - | [[Category: Virus-inhibitor complex]]
| + | |
| Structural highlights
Function
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).[1] Encapsidates hepatitis delta genome (By similarity).[2]
Publication Abstract from PubMed
Hepatitis B virus (HBV) is a major cause of liver disease. Assembly of the HBV capsid is a critical step in virus production and an attractive target for new antiviral therapies. We determined the structure of HBV capsid in complex with AT-130, a member of the phenylpropenamide family of assembly effectors. AT-130 causes tertiary and quaternary structural changes but does not disrupt capsid structure. AT-130 binds a hydrophobic pocket that also accommodates the previously characterized heteroaryldihydropyrimidine compounds but favors a unique quasiequivalent location on the capsid surface. Thus, this pocket is a promiscuous drug-binding site and a likely target for different assembly effectors with a broad range of mechanisms of activity. That AT-130 successfully decreases virus production by increasing capsid assembly rate without disrupting capsid structure delineates a paradigm in antiviral design, that disrupting reaction timing is a viable strategy for assembly effectors of HBV and other viruses.
Assembly-directed antivirals differentially bind quasiequivalent pockets to modify hepatitis B virus capsid tertiary and quaternary structure.,Katen SP, Tan Z, Chirapu SR, Finn MG, Zlotnick A Structure. 2013 Aug 6;21(8):1406-16. doi: 10.1016/j.str.2013.06.013. Epub 2013, Jul 18. PMID:23871485[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wingfield PT, Stahl SJ, Williams RW, Steven AC. Hepatitis core antigen produced in Escherichia coli: subunit composition, conformational analysis, and in vitro capsid assembly. Biochemistry. 1995 Apr 18;34(15):4919-32. PMID:7711014
- ↑ Wingfield PT, Stahl SJ, Williams RW, Steven AC. Hepatitis core antigen produced in Escherichia coli: subunit composition, conformational analysis, and in vitro capsid assembly. Biochemistry. 1995 Apr 18;34(15):4919-32. PMID:7711014
- ↑ Katen SP, Tan Z, Chirapu SR, Finn MG, Zlotnick A. Assembly-directed antivirals differentially bind quasiequivalent pockets to modify hepatitis B virus capsid tertiary and quaternary structure. Structure. 2013 Aug 6;21(8):1406-16. doi: 10.1016/j.str.2013.06.013. Epub 2013, Jul 18. PMID:23871485 doi:10.1016/j.str.2013.06.013
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