8cm8: Difference between revisions
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==Galectin-8 N-terminal carbohydrate recognition domain in complex with 4-(bromophenyl)phthalazinone D-galactal ligand== | |||
<StructureSection load='8cm8' size='340' side='right'caption='[[8cm8]], [[Resolution|resolution]] 1.22Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8cm8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CM8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CM8 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]] 1.22Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=V19:4-(4-bromophenyl)-2-[[(2~{R},3~{R},4~{R})-2-(hydroxymethyl)-3-oxidanyl-3,4-dihydro-2~{H}-pyran-4-yl]oxymethyl]phthalazin-1-one'>V19</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=8cm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cm8 OCA], [https://pdbe.org/8cm8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cm8 RCSB], [https://www.ebi.ac.uk/pdbsum/8cm8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cm8 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LEG8_HUMAN LEG8_HUMAN] Lectin with a marked preference for 3'-O-sialylated and 3'-O-sulfated glycans.<ref>PMID:21288902</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Galectin-8 contains two different carbohydrate recognition domains (CRDs). Selective inhibitors for at least one CRD are desirable for galectin-8 biology studies and potentially for pharmacological purposes. Structure-guided design led to the discovery of potent and selective glycomimetic-heterocycle hybrid ligands, with a 4-(p-bromophenyl)phthalazinone derivative displaying a 34 muM K (d) for galectin-8N (N-terminal CRD), no binding to galectin-8C (C-terminal CRD), -1, -3, -4N, -7, -9C, or -9N, and >40-fold selectivity over galectin-4C. Selectivity was achieved with the halogenated 4-phenylphthalazinone moiety occupying a galectin-8N-specific sub-pocket. A 1.30 A resolution X-ray structure revealed the phthalazinone moiety stacking with Arg45 and the 4-bromophenyl moiety stacking both Arg59 and Tyr141 of galectin-8N. Physicochemical and in vitro ADME studies revealed a desirable LogD, which also translated to good passive permeability. The chemical, microsome, and plasma stability support these compounds as promising tool compounds and candidates for hit-to-lead optimization. | |||
Galectin-8N-Selective 4-Halophenylphthalazinone-Galactals Double pi-Stack in a Unique Pocket.,van Klaveren S, Hassan M, Hakansson M, Johnsson RE, Larsson J, Jakopin Z, Anderluh M, Leffler H, Tomasic T, Nilsson UJ ACS Med Chem Lett. 2024 Jul 22;15(8):1319-1324. doi: , 10.1021/acsmedchemlett.4c00212. eCollection 2024 Aug 8. PMID:39140038<ref>PMID:39140038</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8cm8" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Diehl C]] | |||
[[Category: Hakansson M]] | |||
[[Category: Nilsson NJ]] | |||
[[Category: Van Klaveren S]] | |||
Latest revision as of 06:43, 19 March 2025
Galectin-8 N-terminal carbohydrate recognition domain in complex with 4-(bromophenyl)phthalazinone D-galactal ligand
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