7bcm: Difference between revisions
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==The DDR1 Kinase Domain Bound To SR302== | ==The DDR1 Kinase Domain Bound To SR302== | ||
<StructureSection load='7bcm' size='340' side='right'caption='[[7bcm]]' scene=''> | <StructureSection load='7bcm' size='340' side='right'caption='[[7bcm]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BCM FirstGlance]. <br> | <table><tr><td colspan='2'>[[7bcm]] 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=7BCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BCM FirstGlance]. <br> | ||
</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=7bcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bcm OCA], [https://pdbe.org/7bcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bcm RCSB], [https://www.ebi.ac.uk/pdbsum/7bcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bcm ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TBK:~{N}-[[4-[[(2~{S})-4-cyclohexyl-1-[[(3~{S})-1-methylsulfonylpiperidin-3-yl]amino]-1-oxidanylidene-butan-2-yl]carbamoyl]phenyl]methyl]imidazo[1,2-a]pyridine-3-carboxamide'>TBK</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=7bcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bcm OCA], [https://pdbe.org/7bcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bcm RCSB], [https://www.ebi.ac.uk/pdbsum/7bcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bcm ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/DDR1_HUMAN DDR1_HUMAN]] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Discoidin domain receptors 1 and 2 (DDR1/2) play a central role in fibrotic disorders, such as renal and pulmonary fibrosis, atherosclerosis, and various forms of cancer. Potent and selective inhibitors, so-called chemical probe compounds, have been developed to study DDR1/2 kinase signaling. However, these inhibitors showed undesired activity on other kinases such as the tyrosine protein kinase receptor TIE or tropomyosin receptor kinases, which are related to angiogenesis and neuronal toxicity. In this study, we optimized our recently published p38 mitogen-activated protein kinase inhibitor 7 toward a potent and cell-active dual DDR/p38 chemical probe and developed a structurally related negative control. The structure-guided design approach used provided insights into the P-loop folding process of p38 and how targeting of non-conserved amino acids modulates inhibitor selectivity. The developed and comprehensively characterized DDR/p38 probe, 30 (SR-302), is a valuable tool for studying the role of DDR kinase in normal physiology and in disease development. | |||
Development of a Selective Dual Discoidin Domain Receptor (DDR)/p38 Kinase Chemical Probe.,Rohm S, Berger BT, Schroder M, Chatterjee D, Mathea S, Joerger AC, Pinkas DM, Bufton JC, Tjaden A, Kovooru L, Kudolo M, Pohl C, Bullock AN, Muller S, Laufer S, Knapp S J Med Chem. 2021 Sep 23;64(18):13451-13474. doi: 10.1021/acs.jmedchem.1c00868., Epub 2021 Sep 10. PMID:34506142<ref>PMID:34506142</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7bcm" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Epithelial discoidin domain-containing receptor|Epithelial discoidin domain-containing receptor]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chatterjee D]] | [[Category: Chatterjee D]] | ||
Revision as of 10:00, 14 September 2022
The DDR1 Kinase Domain Bound To SR302The DDR1 Kinase Domain Bound To SR302
Structural highlights
FunctionPublication Abstract from PubMedDiscoidin domain receptors 1 and 2 (DDR1/2) play a central role in fibrotic disorders, such as renal and pulmonary fibrosis, atherosclerosis, and various forms of cancer. Potent and selective inhibitors, so-called chemical probe compounds, have been developed to study DDR1/2 kinase signaling. However, these inhibitors showed undesired activity on other kinases such as the tyrosine protein kinase receptor TIE or tropomyosin receptor kinases, which are related to angiogenesis and neuronal toxicity. In this study, we optimized our recently published p38 mitogen-activated protein kinase inhibitor 7 toward a potent and cell-active dual DDR/p38 chemical probe and developed a structurally related negative control. The structure-guided design approach used provided insights into the P-loop folding process of p38 and how targeting of non-conserved amino acids modulates inhibitor selectivity. The developed and comprehensively characterized DDR/p38 probe, 30 (SR-302), is a valuable tool for studying the role of DDR kinase in normal physiology and in disease development. Development of a Selective Dual Discoidin Domain Receptor (DDR)/p38 Kinase Chemical Probe.,Rohm S, Berger BT, Schroder M, Chatterjee D, Mathea S, Joerger AC, Pinkas DM, Bufton JC, Tjaden A, Kovooru L, Kudolo M, Pohl C, Bullock AN, Muller S, Laufer S, Knapp S J Med Chem. 2021 Sep 23;64(18):13451-13474. doi: 10.1021/acs.jmedchem.1c00868., Epub 2021 Sep 10. PMID:34506142[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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