4e7l: Difference between revisions
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[[ | ==PFV integrase Strand Transfer Complex (STC-Mn*) following reaction in crystallo, at 3.0 A resolution.== | ||
<StructureSection load='4e7l' size='340' side='right' caption='[[4e7l]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4e7l]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_spumaretrovirus Human spumaretrovirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E7L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E7L FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3dlr|3dlr]], [[3oy9|3oy9]], [[3oya|3oya]], [[3os0|3os0]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11963 Human spumaretrovirus])</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4e7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e7l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e7l RCSB], [http://www.ebi.ac.uk/pdbsum/4e7l PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Retroviral integrase (IN) is responsible for two consecutive reactions, which lead to insertion of a viral DNA copy into a host cell chromosome. Initially, the enzyme removes di- or trinucleotides from viral DNA ends to expose 3'-hydroxyls attached to the invariant CA dinucleotides (3'-processing reaction). Second, it inserts the processed 3'-viral DNA ends into host chromosomal DNA (strand transfer). Herein, we report a crystal structure of prototype foamy virus IN bound to viral DNA prior to 3'-processing. Furthermore, taking advantage of its dependence on divalent metal ion cofactors, we were able to freeze trap the viral enzyme in its ground states containing all the components necessary for 3'-processing or strand transfer. Our results shed light on the mechanics of retroviral DNA integration and explain why HIV IN strand transfer inhibitors are ineffective against the 3'-processing step of integration. The ground state structures moreover highlight a striking substrate mimicry utilized by the inhibitors in their binding to the IN active site and suggest ways to improve upon this clinically relevant class of small molecules. | |||
3'-Processing and strand transfer catalysed by retroviral integrase in crystallo.,Hare S, Maertens GN, Cherepanov P EMBO J. 2012 May 11. doi: 10.1038/emboj.2012.118. PMID:22580823<ref>PMID:22580823</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
< | |||
[[Category: Human spumaretrovirus]] | [[Category: Human spumaretrovirus]] | ||
[[Category: Cherepanov, P.]] | [[Category: Cherepanov, P.]] | ||
Revision as of 10:58, 5 June 2014
PFV integrase Strand Transfer Complex (STC-Mn*) following reaction in crystallo, at 3.0 A resolution.PFV integrase Strand Transfer Complex (STC-Mn*) following reaction in crystallo, at 3.0 A resolution.
Structural highlights
Publication Abstract from PubMedRetroviral integrase (IN) is responsible for two consecutive reactions, which lead to insertion of a viral DNA copy into a host cell chromosome. Initially, the enzyme removes di- or trinucleotides from viral DNA ends to expose 3'-hydroxyls attached to the invariant CA dinucleotides (3'-processing reaction). Second, it inserts the processed 3'-viral DNA ends into host chromosomal DNA (strand transfer). Herein, we report a crystal structure of prototype foamy virus IN bound to viral DNA prior to 3'-processing. Furthermore, taking advantage of its dependence on divalent metal ion cofactors, we were able to freeze trap the viral enzyme in its ground states containing all the components necessary for 3'-processing or strand transfer. Our results shed light on the mechanics of retroviral DNA integration and explain why HIV IN strand transfer inhibitors are ineffective against the 3'-processing step of integration. The ground state structures moreover highlight a striking substrate mimicry utilized by the inhibitors in their binding to the IN active site and suggest ways to improve upon this clinically relevant class of small molecules. 3'-Processing and strand transfer catalysed by retroviral integrase in crystallo.,Hare S, Maertens GN, Cherepanov P EMBO J. 2012 May 11. doi: 10.1038/emboj.2012.118. PMID:22580823[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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