7rsx
From Proteopedia
(Difference between revisions)
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<table><tr><td colspan='2'>[[7rsx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RSX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RSX FirstGlance]. <br> | <table><tr><td colspan='2'>[[7rsx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RSX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RSX FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7IT: | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7IT:~{N}-[(1~{R},2~{R},3~{S})-3-[(3~{S})-3,4-bis(oxidanyl)butyl]-2-(carbamimidamidomethyl)-5-(methylaminomethyl)-2,3-dihydro-1~{H}-inden-1-yl]-~{N}-(4-chloranyl-3-fluoranyl-phenyl)ethanediamide'>7IT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7rsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rsx OCA], [https://pdbe.org/7rsx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rsx RCSB], [https://www.ebi.ac.uk/pdbsum/7rsx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rsx ProSAT]</span></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=7rsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rsx OCA], [https://pdbe.org/7rsx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rsx RCSB], [https://www.ebi.ac.uk/pdbsum/7rsx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rsx ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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The design and synthesis of butyl chain derivatives at the indane ring 3-position of our lead CD4-mimetic compound BNM-III-170 that inhibits human immunodeficiency virus (HIV-1) infection are reported. Optimization efforts were guided by crystallographic and computational analysis of the small-molecule ligands of the Phe43 cavity of the envelope glycoprotein gp120. Biological evaluation of 11-21 revealed that members of this series of CD4-mimetic compounds are able to inhibit HIV-1 viral entry into target cells more potently and with greater breadth compared to BNM-III-170. Crystallographic analysis of the binding pocket of 14, 16, and 17 revealed a novel hydrogen bonding interaction between His105 and a primary hydroxyl group on the butyl side chain. Further optimization of this interaction with the His105 residue holds the promise of more potent CD4-mimetic compounds. | The design and synthesis of butyl chain derivatives at the indane ring 3-position of our lead CD4-mimetic compound BNM-III-170 that inhibits human immunodeficiency virus (HIV-1) infection are reported. Optimization efforts were guided by crystallographic and computational analysis of the small-molecule ligands of the Phe43 cavity of the envelope glycoprotein gp120. Biological evaluation of 11-21 revealed that members of this series of CD4-mimetic compounds are able to inhibit HIV-1 viral entry into target cells more potently and with greater breadth compared to BNM-III-170. Crystallographic analysis of the binding pocket of 14, 16, and 17 revealed a novel hydrogen bonding interaction between His105 and a primary hydroxyl group on the butyl side chain. Further optimization of this interaction with the His105 residue holds the promise of more potent CD4-mimetic compounds. | ||
| - | Identification of gp120 Residue His105 as a Novel Target for HIV-1 Neutralization by Small-Molecule CD4-Mimics.,Fritschi CJ, Liang S, Mohammadi M, Anang S, Moraca F, Chen J, Madani N, Sodroski JG, Abrams CF, Hendrickson WA, Smith AB 3rd ACS Med Chem Lett. 2021 Oct 29;12(11):1824-1831. doi:, 10.1021/acsmedchemlett.1c00437. eCollection 2021 Nov 11. PMID:34795873<ref>PMID:34795873</ref> | + | Identification of gp120 Residue His105 as a Novel Target for HIV-1 Neutralization by Small-Molecule CD4-Mimics.,Fritschi CJ, Liang S, Mohammadi M, Anang S, Moraca F, Chen J, Madani N, Sodroski JG, Abrams CF, Hendrickson WA, Smith AB 3rd ACS Med Chem Lett. 2021 Oct 29;12(11):1824-1831. doi: , 10.1021/acsmedchemlett.1c00437. eCollection 2021 Nov 11. PMID:34795873<ref>PMID:34795873</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
HIV-1 gp120 complex with CJF-III-049-S
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