This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


6akx

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "6akx" [edit=sysop:move=sysop])
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 6akx is ON HOLD
+
==The Crystal structure of Human Chemokine Receptor CCR5 in complex with compound 21==
 +
<StructureSection load='6akx' size='340' side='right' caption='[[6akx]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[6akx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AKX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AKX FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A4R:N-[(1S)-3-{(3-exo)-3-[3-methyl-5-(propan-2-yl)-4H-1,2,4-triazol-4-yl]-8-azabicyclo[3.2.1]octan-8-yl}-1-(thiophen-2-yl)propyl]cyclopentanecarboxamide'>A4R</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6akx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6akx OCA], [http://pdbe.org/6akx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6akx RCSB], [http://www.ebi.ac.uk/pdbsum/6akx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6akx ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[[http://www.uniprot.org/uniprot/CCR5_HUMAN CCR5_HUMAN]] Genetic variation in CCR5 is associated with susceptibility to diabetes mellitus insulin-dependent type 22 (IDDM22) [MIM:[http://omim.org/entry/612522 612522]]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:19073967</ref>
 +
== Function ==
 +
[[http://www.uniprot.org/uniprot/CCR5_HUMAN CCR5_HUMAN]] Receptor for a number of inflammatory CC-chemokines including MIP-1-alpha, MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation. Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 R5 isolates.<ref>PMID:8639485</ref> <ref>PMID:8663314</ref> <ref>PMID:8699119</ref> <ref>PMID:8649511</ref> <ref>PMID:8649512</ref> <ref>PMID:11323418</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
CC-chemokine receptor 5 (CCR5) is an attractive target for preventing the entry of human immunodeficiency virus 1 (HIV-1) into human host cells. Maraviroc is the only CCR5 antagonist, and it was marketed in 2007. To overcome the shortcomings of maraviroc, structure-based drug design was performed to minimize CYP450 inhibition and to enhance anti-HIV potency and bioavailability. Thirty-four novel 1-heteroaryl-1,3-propanediamine derivatives (1-34) were synthesized, displaying CCR5-antagonist activities in the 2.3-296.4 nM range. Among these, compounds 21 and 34 were the most potent CCR5 antagonists, with excellent in vitro anti-HIV-1 activity, low cytotoxicity, and an acceptable pharmacokinetic profile. Furthermore, the X-ray crystal structures of compounds 21 and 34 bound to CCR5 were determined at 2.8 A resolution. Compound 34 exhibited no CYP450-inhibition activity at 25 muM, which overcomes the potential drug-drug interaction of maraviroc. Compound 34 represents a promising drug candidate for HIV-infection treatment.
-
Authors:
+
Structure-Based Design of 1-Heteroaryl-1,3-propanediamine Derivatives as a Novel Series of CC-Chemokine Receptor 5 Antagonists.,Peng P, Chen H, Zhu Y, Wang Z, Li J, Luo RH, Wang J, Chen L, Yang LM, Jiang H, Xie X, Wu B, Zheng YT, Liu H J Med Chem. 2018 Oct 17. doi: 10.1021/acs.jmedchem.8b01077. PMID:30234300<ref>PMID:30234300</ref>
-
Description:
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
 +
<div class="pdbe-citations 6akx" style="background-color:#fffaf0;"></div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Wu, B]]
 +
[[Category: Zhao, Q]]
 +
[[Category: Zhu, Y]]
 +
[[Category: G protein-coupled receptor chemokine receptor ccr5 antagonist complex structure]]
 +
[[Category: Signaling protein]]

Revision as of 05:49, 24 October 2018

The Crystal structure of Human Chemokine Receptor CCR5 in complex with compound 21

6akx, resolution 2.80Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6akx"
Personal tools