5hfl: Difference between revisions
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==Gp41-targeting HIV-1 fusion inhibitors with helical Ile-Asp-Leu tail== | |||
<StructureSection load='5hfl' size='340' side='right' caption='[[5hfl]], [[Resolution|resolution]] 2.29Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5hfl]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HFL FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hfm|5hfm]]</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=5hfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hfl OCA], [http://pdbe.org/5hfl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hfl RCSB], [http://www.ebi.ac.uk/pdbsum/5hfl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hfl ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Peptides derived from the C-terminal heptad repeat (CHR) of HIV gp41 have been developed as effective fusion inhibitors against HIV-1, but facing the challenges of enhancing potency and stability. Here, we report a rationally designed novel HIV-1 fusion inhibitor derived from CHR-derived peptide (Trp628~Gln653, named CP), but with an innovative Ile-Asp-Leu tail (IDL) that dramatically increased the inhibitory activity by up to 100 folds. We also determined the crystal structures of artificial fusion peptides N36- and N43-L6-CP-IDL. Although the overall structures of both fusion peptides share the canonical six-helix bundle (6-HB) configuration, their IDL tails adopt two different conformations: a one-turn helix with the N36, and a hook-like structure with the longer N43. Structural comparison showed that the hook-like IDL tail possesses a larger interaction interface with NHR than the helical one. Further molecular dynamics simulations of the two 6-HBs and isolated CP-IDL peptides suggested that hook-like form of IDL tail can be stabilized by its binding to NHR trimer. Therefore, CP-IDL has potential for further development as a new HIV fusion inhibitor, and this strategy could be widely used in developing artificial fusion inhibitors against HIV and other enveloped viruses. | |||
Rational improvement of gp41-targeting HIV-1 fusion inhibitors: an innovatively designed Ile-Asp-Leu tail with alternative conformations.,Zhu Y, Su S, Qin L, Wang Q, Shi L, Ma Z, Tang J, Jiang S, Lu L, Ye S, Zhang R Sci Rep. 2016 Sep 26;6:31983. doi: 10.1038/srep31983. PMID:27666394<ref>PMID:27666394</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5hfl" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Ye, S]] | |||
[[Category: Zhang, R]] | |||
[[Category: Zhu, Y]] | |||
[[Category: Fusion inhibitor]] | |||
[[Category: Helical tail]] | |||
[[Category: Hiv-1]] | |||
[[Category: Ile-asp-leu tail]] | |||
[[Category: Viral protein]] | |||
Revision as of 16:27, 18 January 2017
Gp41-targeting HIV-1 fusion inhibitors with helical Ile-Asp-Leu tail
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