6j10
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='6j10' size='340' side='right'caption='[[6j10]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='6j10' size='340' side='right'caption='[[6j10]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6j10]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J10 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6J10 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6j10]] is a 6 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=6J10 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6J10 FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B4O:6-cyclohexyl-4-methyl-1-oxidanyl-pyridin-2-one'>B4O</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B4O:6-cyclohexyl-4-methyl-1-oxidanyl-pyridin-2-one'>B4O</scene></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=6j10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j10 OCA], [http://pdbe.org/6j10 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6j10 RCSB], [http://www.ebi.ac.uk/pdbsum/6j10 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6j10 ProSAT]</span></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=6j10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j10 OCA], [http://pdbe.org/6j10 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6j10 RCSB], [http://www.ebi.ac.uk/pdbsum/6j10 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6j10 ProSAT]</span></td></tr> | ||
| Line 9: | Line 9: | ||
== 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> | [[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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Chronic hepatitis B virus (HBV) infection can cause cirrhosis and hepatocellular carcinoma and is therefore a serious public health problem. Infected patients are currently treated with nucleoside/nucleotide analogs and interferon alpha, but this approach is not curative. Here, we screen 978 FDA-approved compounds for their ability to inhibit HBV replication in HBV-expressing HepG2.2.15 cells. We find that ciclopirox, a synthetic antifungal agent, strongly inhibits HBV replication in cells and in mice by blocking HBV capsid assembly. The crystal structure of the HBV core protein and ciclopirox complex reveals a unique binding mode at dimer-dimer interfaces. Ciclopirox synergizes with nucleoside/nucleotide analogs to prevent HBV replication in cells and in a humanized liver mouse model. Therefore, orally-administered ciclopirox may provide a novel opportunity to combat chronic HBV infection by blocking HBV capsid assembly. | ||
| + | |||
| + | Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly.,Kang JA, Kim S, Park M, Park HJ, Kim JH, Park S, Hwang JR, Kim YC, Jun Kim Y, Cho Y, Sun Jin M, Park SG Nat Commun. 2019 May 16;10(1):2184. doi: 10.1038/s41467-019-10200-5. PMID:31097716<ref>PMID:31097716</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6j10" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Hbv-d]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cho, Y]] | [[Category: Cho, Y]] | ||
Revision as of 06:36, 29 May 2019
Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly
| |||||||||||
Categories: Hbv-d | Large Structures | Cho, Y | Hwang, J | Jin, M S | Kang, J | Kim, J | Kim, S | Kim, Y | Kim, Y J | Park, H | Park, M | Park, S | Capsid assembly inhibitor | Ciclopirox | Hepatitis b virus | Viral protein
