View source for 4dkq


==Crystal structure of clade A/E 93TH057 HIV-1 gp120 core in complex with DMJ-I-228==
<StructureSection load='4dkq' size='340' side='right'caption='[[4dkq]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4dkq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(BRU_ISOLATE) Human immunodeficiency virus type 1 (BRU ISOLATE)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DKQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DKQ 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]] 1.888&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0LK:N-[(1S,2S)-2-CARBAMIMIDAMIDO-2,3-DIHYDRO-1H-INDEN-1-YL]-N-(4-CHLORO-3-FLUOROPHENYL)ETHANEDIAMIDE'>0LK</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</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=4dkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dkq OCA], [https://pdbe.org/4dkq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dkq RCSB], [https://www.ebi.ac.uk/pdbsum/4dkq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dkq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q0ED31_9HIV1 Q0ED31_9HIV1] The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface (By similarity).[RuleBase:RU004292][SAAS:SAAS000328_004_020447]  The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cellular infection by HIV-1 is initiated with a binding event between the viral envelope glycoprotein gp120 and the cellular receptor protein CD4. The CD4-gp120 interface is dominated by two hotspots: a hydrophobic gp120 cavity capped by Phe43(CD4) and an electrostatic interaction between residues Arg59(CD4) and Asp368(gp120). The CD4 mimetic small-molecule NBD-556 (1) binds within the gp120 cavity; however, 1 and related congeners demonstrate limited viral neutralization breadth. Herein, we report the design, synthesis, characterization, and X-ray structures of gp120 in complex with small molecules that simultaneously engage both binding hotspots. The compounds specifically inhibit viral infection of 42 tier 2 clades B and C viruses and are shown to be antagonists of entry into CD4-negative cells. Dual hotspot design thus provides both a means to enhance neutralization potency of HIV-1 entry inhibitors and a novel structural paradigm for inhibiting the CD4-gp120 protein-protein interaction.

Structure-Based Design, Synthesis, and Characterization of Dual Hotspot Small-Molecule HIV-1 Entry Inhibitors.,Lalonde JM, Kwon YD, Jones DM, Sun AW, Courter JR, Soeta T, Kobayashi T, Princiotto AM, Wu X, Schon A, Freire E, Kwong PD, Mascola JR, Sodroski J, Madani N, Smith AB 3rd J Med Chem. 2012 Apr 23. PMID:22497421<ref>PMID:22497421</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4dkq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Gp120 3D structures|Gp120 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Courter JR]]
[[Category: Freire E]]
[[Category: Jones DM]]
[[Category: Kobayashi T]]
[[Category: Kwon YD]]
[[Category: Kwong PD]]
[[Category: LaLonde JM]]
[[Category: Madani N]]
[[Category: Mascola J]]
[[Category: Princiotto AM]]
[[Category: Schon A]]
[[Category: Smith III AB]]
[[Category: Sodroski J]]
[[Category: Soeta T]]
[[Category: Sun AW]]
[[Category: Wu X]]