9rko: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 9rko is ~~ON HOLD~~

==Langerin in complex with Thiazolopyrimidine==

== Structural highlights ==

<table><tr><td colspan='2'>[[9rko]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9RKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9RKO 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]] 1.89Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1JHV:2,3-dimethyl-5-oxidanylidene-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylic+acid'>A1JHV</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=9rko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9rko OCA], [https://pdbe.org/9rko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9rko RCSB], [https://www.ebi.ac.uk/pdbsum/9rko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9rko ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/CLC4K_MOUSE CLC4K_MOUSE] Calcium-dependent lectin displaying mannose-binding specificity. Induces the formation of Birbeck granules (BGs); is a potent regulator of membrane superimposition and zippering. Binds to sulfated as well as mannosylated glycans, keratan sulfate (KS) and beta-glucans. Facilitates uptake of antigens and is involved in the routing and/or processing of antigen for presentation to T cells.<ref>PMID:11777972</ref> <ref>PMID:18322168</ref>

== Publication Abstract from PubMed ==

C-Type lectins are a large family of carbohydrate-binding proteins. Langerin is a member of this family and is expressed by Langerhans cells, involved in pathogen recognition and innate immune activation, making it a target for small-molecule modulation in immunology and infectious diseases. We previously identified thiazolopyrimidinones as a series of allosteric inhibitors, but the underlying mechanism remained unclear. In this study, (43)Ca NMR demonstrated that these fragments induce Ca(2+) release from the receptor. Our ITC data suggested a competitive relationship between inhibitors and Ca(2+), which was further validated by (19)F NMR spectroscopy showing inhibition of carbohydrate binding. Surprisingly, the fragment binding site was found to be located beneath the long loop, which supports the dynamic nature of the long loop being highly Ca(2+) dependent. Our findings provide insight into the novel Ca(2+)-competitive inhibitory mechanism of murine langerin and are the first report on such an inhibitory mechanism for a C-type lectin.

~~Authors~~:

Calcium Competitive Inhibition of Langerin by Thiazolopyrimidinones.,Ning Y, Efrem NL, Amoussa M, Turhan E, Zheng D, Lefebre J, Ruwolt M, Neu U, Besch M, Loll B, Kurzbach D, Kohnke J, Nazare M, Rademacher C J Med Chem. 2025 Dec 11;68(23):24924-24934. doi: 10.1021/acs.jmedchem.5c01756. , Epub 2025 Nov 19. PMID:41261040<ref>PMID:41261040</ref>

~~Description~~:

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

[[Category: ~~Unreleased~~ Structures]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Large Structures]]

[[Category: Mus musculus]]

[[Category: Koehnke J]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9rko is ON HOLD
+==Langerin in complex with Thiazolopyrimidine==
+<StructureSection load='9rko' size='340' side='right'caption='[[9rko]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9rko]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9RKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9RKO 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]] 1.89&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1JHV:2,3-dimethyl-5-oxidanylidene-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylic+acid'>A1JHV</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=9rko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9rko OCA], [https://pdbe.org/9rko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9rko RCSB], [https://www.ebi.ac.uk/pdbsum/9rko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9rko ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CLC4K_MOUSE CLC4K_MOUSE] Calcium-dependent lectin displaying mannose-binding specificity. Induces the formation of Birbeck granules (BGs); is a potent regulator of membrane superimposition and zippering. Binds to sulfated as well as mannosylated glycans, keratan sulfate (KS) and beta-glucans. Facilitates uptake of antigens and is involved in the routing and/or processing of antigen for presentation to T cells.<ref>PMID:11777972</ref> <ref>PMID:18322168</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+C-Type lectins are a large family of carbohydrate-binding proteins. Langerin is a member of this family and is expressed by Langerhans cells, involved in pathogen recognition and innate immune activation, making it a target for small-molecule modulation in immunology and infectious diseases. We previously identified thiazolopyrimidinones as a series of allosteric inhibitors, but the underlying mechanism remained unclear. In this study, (43)Ca NMR demonstrated that these fragments induce Ca(2+) release from the receptor. Our ITC data suggested a competitive relationship between inhibitors and Ca(2+), which was further validated by (19)F NMR spectroscopy showing inhibition of carbohydrate binding. Surprisingly, the fragment binding site was found to be located beneath the long loop, which supports the dynamic nature of the long loop being highly Ca(2+) dependent. Our findings provide insight into the novel Ca(2+)-competitive inhibitory mechanism of murine langerin and are the first report on such an inhibitory mechanism for a C-type lectin.
-Authors:
+Calcium Competitive Inhibition of Langerin by Thiazolopyrimidinones.,Ning Y, Efrem NL, Amoussa M, Turhan E, Zheng D, Lefebre J, Ruwolt M, Neu U, Besch M, Loll B, Kurzbach D, Kohnke J, Nazare M, Rademacher C J Med Chem. 2025 Dec 11;68(23):24924-24934. doi: 10.1021/acs.jmedchem.5c01756. , Epub 2025 Nov 19. PMID:41261040<ref>PMID:41261040</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 9rko" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Koehnke J]]