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7p1m

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Current revision

Galectin-8 N-terminal carbohydrate recognition domain in complex with benzimidazole D-galactal ligand

Structural highlights

7p1m is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.52Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LEG8_HUMAN Lectin with a marked preference for 3'-O-sialylated and 3'-O-sulfated glycans.^[1]

Publication Abstract from PubMed

Galectin-8 is a carbohydrate-binding protein that plays a crucial role in tumor progression and metastasis, antibacterial autophagy, modulation of the immune system, and bone remodeling. The design, synthesis, and protein affinity evaluation of a set of C-3 substituted benzimidazole and quinoline d-galactal derivatives identified a d-galactal-benzimidazole hybrid as a selective ligand for the galectin-8 N-terminal domain (galectin-8N), with a K d of 48 muM and 15-fold selectivity over galectin-3 and even better selectivity over the other mammalian galectins. X-ray structural analysis of galectin-8N in complex with one benzimidazole- and one quinoline-galactal derivative at 1.52 and 2.1 A together with molecular dynamics simulations and quantum mechanical calculations of galectin-8N in complex with the benzimidazole derivative revealed orbital overlap between a NH LUMO of Arg45 with electron rich HOMOs of the olefin and O4 of the d-galactal. Such overlap is hypothesized to contribute to the high affinity of the d-galactal-derived ligands for galectin-8N. A (3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay evaluation of the d-galactal-benzimidazole hybrid and an analogous galactoside derivative on a panel of cell lines with MTS assay showed no effect on cell viability up to 100 muM concentration. A subsequent functional assay using the MDA-MB-231 cell line demonstrated that the d-galactal-benzimidazole hybrid and the analogous galactoside derivative reduced the secretion of the proinflammatory cytokines interleukin-6 (IL-6) and IL-8 in a dose-dependent manner. Therefore, these compounds represent potential probes for galectin-8N pharmacology investigations and possibly promising leads for the design and synthesis of potent and selective galectin-8 inhibitors as potential antitumor and anti-inflammatory agents.

Structure-Guided Design of d-Galactal Derivatives with High Affinity and Selectivity for the Galectin-8 N-Terminal Domain.,Hassan M, Baussiere F, Guzelj S, Sundin AP, Hakansson M, Kovacic R, Leffler H, Tomasic T, Anderluh M, Jakopin Z, Nilsson UJ ACS Med Chem Lett. 2021 Nov 2;12(11):1745-1752. doi:, 10.1021/acsmedchemlett.1c00371. eCollection 2021 Nov 11. PMID:34795863^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ideo H, Matsuzaka T, Nonaka T, Seko A, Yamashita K. Galectin-8-N-domain recognition mechanism for sialylated and sulfated glycans. J Biol Chem. 2011 Apr 1;286(13):11346-55. Epub 2011 Feb 2. PMID:21288902 doi:10.1074/jbc.M110.195925
↑ Hassan M, Baussiere F, Guzelj S, Sundin AP, Hakansson M, Kovacic R, Leffler H, Tomasic T, Anderluh M, Jakopin Z, Nilsson UJ. Structure-Guided Design of d-Galactal Derivatives with High Affinity and Selectivity for the Galectin-8 N-Terminal Domain. ACS Med Chem Lett. 2021 Nov 2;12(11):1745-1752. doi:, 10.1021/acsmedchemlett.1c00371. eCollection 2021 Nov 11. PMID:34795863 doi:http://dx.doi.org/10.1021/acsmedchemlett.1c00371

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7p1m"

@@ Line 3: / Line 3: @@
 <StructureSection load='7p1m' size='340' side='right'caption='[[7p1m]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7p1m]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P1M FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7p1m]] 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=7P1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P1M FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4IU:2-[[(2R,3R,4R)-2-(hydroxymethyl)-3-oxidanyl-3,4-dihydro-2H-pyran-4-yl]oxymethyl]-3-methyl-benzimidazole-5-carboxylic+acid'>4IU</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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]] 1.52&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4IU:2-[[(2R,3R,4R)-2-(hydroxymethyl)-3-oxidanyl-3,4-dihydro-2H-pyran-4-yl]oxymethyl]-3-methyl-benzimidazole-5-carboxylic+acid'>4IU</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=7p1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p1m OCA], [https://pdbe.org/7p1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p1m RCSB], [https://www.ebi.ac.uk/pdbsum/7p1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p1m 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>
+[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 ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 7p1m" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Galectin 3D structures|Galectin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Hakansson, M]]
+[[Category: Hakansson M]]
-[[Category: Hassan, M]]
+[[Category: Hassan M]]
-[[Category: Kovacic, R]]
+[[Category: Kovacic R]]
-[[Category: Nilsson, J U]]
+[[Category: Nilsson JU]]
-[[Category: Complex]]
-[[Category: D-galactal]]
-[[Category: Galectin]]
-[[Category: Inhibitor]]
-[[Category: Lectin]]
-[[Category: Sugar binding protein]]

7p1m

From Proteopedia

Current revision

Galectin-8 N-terminal carbohydrate recognition domain in complex with benzimidazole D-galactal ligand

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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