8p1o

From Proteopedia

(Difference between revisions)

Revision as of 11:43, 1 February 2024

Solubilizer tag effect on PD-L1/inhibitor binding properties for m-terphenyl derivatives

Structural highlights

8p1o 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 2.17Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PD1L1_HUMAN Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation and cytokine production.^[1] ^[2]

Publication Abstract from PubMed

Although heavily studied, the subject of anti-PD-L1 small-molecule inhibitors is still elusive. Here we present a systematic overview of the principles behind successful anti-PD-L1 small-molecule inhibitor design on the example of the m-terphenyl scaffold, with a particular focus on the neglected influence of the solubilizer tag on the overall affinity toward PD-L1. The inhibitor developed according to the proposed guidelines was characterized through its potency in blocking PD-1/PD-L1 complex formation in homogeneous time-resolved fluorescence and cell-based assays. The affinity is also explained based on the crystal structure of the inhibitor itself and its costructure with PD-L1 as well as a molecular modeling study. Our results structuralize the knowledge related to the strong pharmacophore feature of the m-terphenyl scaffold preferential geometry and the more complex role of the solubilizer tag in PD-L1 homodimer stabilization.

Solubilizer Tag Effect on PD-L1/Inhibitor Binding Properties for m-Terphenyl Derivatives.,Surmiak E, Zaber J, Plewka J, Wojtanowicz G, Kocik-Krol J, Kruc O, Muszak D, Rodriguez I, Musielak B, Viviano M, Castellano S, Skalniak L, Magiera-Mularz K, Holak TA, Kalinowska-Tluscik J ACS Med Chem Lett. 2023 Dec 14;15(1):36-44. doi: 10.1021/acsmedchemlett.3c00306. , eCollection 2024 Jan 11. PMID:38229762^[3]

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

References

↑ Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999 Dec;5(12):1365-9. PMID:10581077 doi:10.1038/70932
↑ Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000 Oct 2;192(7):1027-34. PMID:11015443
↑ Surmiak E, Ząber J, Plewka J, Wojtanowicz G, Kocik-Krol J, Kruc O, Muszak D, Rodríguez I, Musielak B, Viviano M, Castellano S, Skalniak L, Magiera-Mularz K, Holak TA, Kalinowska-Tłuścik J. Solubilizer Tag Effect on PD-L1/Inhibitor Binding Properties for m-Terphenyl Derivatives. ACS Med Chem Lett. 2023 Dec 14;15(1):36-44. PMID:38229762 doi:10.1021/acsmedchemlett.3c00306

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/8p1o"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8p1o is ON HOLD  until Paper Publication
+==Solubilizer tag effect on PD-L1/inhibitor binding properties for m-terphenyl derivatives==
+<StructureSection load='8p1o' size='340' side='right'caption='[[8p1o]], [[Resolution|resolution]] 2.17&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8p1o]] 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=8P1O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8P1O 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]] 2.17&#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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=WEW:(3~{R})-1-[[4-[2-chloranyl-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxy-phenyl]methyl]-~{N}-(2-hydroxyethyl)pyrrolidine-3-carboxamide'>WEW</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=8p1o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8p1o OCA], [https://pdbe.org/8p1o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8p1o RCSB], [https://www.ebi.ac.uk/pdbsum/8p1o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8p1o ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PD1L1_HUMAN PD1L1_HUMAN] Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation and cytokine production.<ref>PMID:10581077</ref> <ref>PMID:11015443</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Although heavily studied, the subject of anti-PD-L1 small-molecule inhibitors is still elusive. Here we present a systematic overview of the principles behind successful anti-PD-L1 small-molecule inhibitor design on the example of the m-terphenyl scaffold, with a particular focus on the neglected influence of the solubilizer tag on the overall affinity toward PD-L1. The inhibitor developed according to the proposed guidelines was characterized through its potency in blocking PD-1/PD-L1 complex formation in homogeneous time-resolved fluorescence and cell-based assays. The affinity is also explained based on the crystal structure of the inhibitor itself and its costructure with PD-L1 as well as a molecular modeling study. Our results structuralize the knowledge related to the strong pharmacophore feature of the m-terphenyl scaffold preferential geometry and the more complex role of the solubilizer tag in PD-L1 homodimer stabilization.
-Authors:
+Solubilizer Tag Effect on PD-L1/Inhibitor Binding Properties for m-Terphenyl Derivatives.,Surmiak E, Zaber J, Plewka J, Wojtanowicz G, Kocik-Krol J, Kruc O, Muszak D, Rodriguez I, Musielak B, Viviano M, Castellano S, Skalniak L, Magiera-Mularz K, Holak TA, Kalinowska-Tluscik J ACS Med Chem Lett. 2023 Dec 14;15(1):36-44. doi: 10.1021/acsmedchemlett.3c00306. , eCollection 2024 Jan 11. PMID:38229762<ref>PMID:38229762</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 8p1o" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Holak TA]]
+[[Category: Kalinowska-Tluscik J]]
+[[Category: Magiera-Mularz K]]
+[[Category: Plewka J]]
+[[Category: Surmiak E]]

8p1o

From Proteopedia

Revision as of 11:43, 1 February 2024

Solubilizer tag effect on PD-L1/inhibitor binding properties for m-terphenyl derivatives

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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