View source for 9fxz


==Galectin-8 N-terminal carbohydrate recognition domain in complex with 4-(bromophenyl)phthalazinone D-galactal ligand==
<StructureSection load='9fxz' size='340' side='right'caption='[[9fxz]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9fxz]] 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=9FXZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FXZ 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]] 1.3&#8491;</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=9fxz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fxz OCA], [https://pdbe.org/9fxz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fxz RCSB], [https://www.ebi.ac.uk/pdbsum/9fxz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fxz 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 &gt;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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9fxz" 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]]