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.

7m3z

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Structure of TIM-3 in complex with N-(4-(8-chloro-2-mehtyl-5-oxo-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolin-9-yl)-3-methylphenyl)methanesulfonamdide (compound 35)

Structural highlights

7m3z is a 1 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 1.4Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HAVR2_HUMAN Regulates macrophage activation. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance. May be also involved in T-cell homing. Receptor for LGALS9.^[1] ^[2]

Publication Abstract from PubMed

T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3; HAVCR2) has emerged as an attractive immune checkpoint target for cancer immunotherapy. TIM-3 is a negative regulator of the systemic immune response to cancer and is expressed on several dysfunctional, or exhausted, immune cell subsets. Upregulation of TIM-3 is associated with tumor progression, poor survival rates, and acquired resistance to antibody-based immunotherapies in the clinic. Despite the potential advantages of small-molecule inhibitors over antibodies, the discovery of small-molecule inhibitors has lagged behind that of antibody therapeutics. Here, we describe the discovery of high-affinity small-molecule ligands for TIM-3 through an NMR-based fragment screen and structure-based lead optimization. These compounds represent useful tools to further study the biology of TIM-3 immune modulation in cancer and serve as a potentially useful starting point toward the discovery of TIM-3-targeted therapeutics.

Fragment-Based Discovery of Small Molecules Bound to T-Cell Immunoglobulin and Mucin Domain-Containing Molecule 3 (TIM-3).,Rietz TA, Teuscher KB, Mills JJ, Gogliotti RD, Lepovitz LT, Scaggs WR, Yoshida K, Luong K, Lee T, Fesik SW J Med Chem. 2021 Oct 1. doi: 10.1021/acs.jmedchem.1c01336. PMID:34597046^[3]

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

References

↑ Sanchez-Fueyo A, Tian J, Picarella D, Domenig C, Zheng XX, Sabatos CA, Manlongat N, Bender O, Kamradt T, Kuchroo VK, Gutierrez-Ramos JC, Coyle AJ, Strom TB. Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance. Nat Immunol. 2003 Nov;4(11):1093-101. Epub 2003 Oct 12. PMID:14556005 doi:http://dx.doi.org/10.1038/ni987
↑ Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005 Dec;6(12):1245-52. Epub 2005 Nov 13. PMID:16286920 doi:http://dx.doi.org/10.1038/ni1271
↑ Rietz TA, Teuscher KB, Mills JJ, Gogliotti RD, Lepovitz LT, Scaggs WR, Yoshida K, Luong K, Lee T, Fesik SW. Fragment-Based Discovery of Small Molecules Bound to T-Cell Immunoglobulin and Mucin Domain-Containing Molecule 3 (TIM-3). J Med Chem. 2021 Oct 1. doi: 10.1021/acs.jmedchem.1c01336. PMID:34597046 doi:http://dx.doi.org/10.1021/acs.jmedchem.1c01336

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7m3z"

Categories: Homo sapiens | Large Structures | Rietz TA

@@ Line 3: / Line 3: @@
 <StructureSection load='7m3z' size='340' side='right'caption='[[7m3z]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7m3z]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7M3Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M3Z FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7m3z]] is a 1 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=7M3Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M3Z FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=YQD:N-{4-[(4S,10aP)-8-chloro-2-methyl-5-oxo-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazolin-9-yl]-3-methylphenyl}methanesulfonamide'>YQD</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]] 1.4&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7m3y|7m3y]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=YQD:N-{4-[(4S,10aP)-8-chloro-2-methyl-5-oxo-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazolin-9-yl]-3-methylphenyl}methanesulfonamide'>YQD</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=7m3z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m3z OCA], [https://pdbe.org/7m3z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m3z RCSB], [https://www.ebi.ac.uk/pdbsum/7m3z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m3z ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/HAVR2_HUMAN HAVR2_HUMAN]] Regulates macrophage activation. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance. May be also involved in T-cell homing. Receptor for LGALS9.<ref>PMID:14556005</ref> <ref>PMID:16286920</ref>
+[https://www.uniprot.org/uniprot/HAVR2_HUMAN HAVR2_HUMAN] Regulates macrophage activation. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance. May be also involved in T-cell homing. Receptor for LGALS9.<ref>PMID:14556005</ref> <ref>PMID:16286920</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Rietz, T A]]
+[[Category: Rietz TA]]
-[[Category: Igv]]
-[[Category: Immune system]]

7m3z

From Proteopedia

Current revision

Structure of TIM-3 in complex with N-(4-(8-chloro-2-mehtyl-5-oxo-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolin-9-yl)-3-methylphenyl)methanesulfonamdide (compound 35)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox