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==The 1.9A crystal structure of humanized Xenopus MDM2 with RO5313109 - a pyrrolidine MDM2 inhibitor== | ==The 1.9A crystal structure of humanized Xenopus MDM2 with RO5313109 - a pyrrolidine MDM2 inhibitor== | ||
<StructureSection load='4jrg' size='340' side='right' caption='[[4jrg]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='4jrg' size='340' side='right'caption='[[4jrg]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4jrg]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4jrg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JRG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JRG FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I09:(3R,4R,5S)-3-(3-CHLOROPHENYL)-4-(4-CHLOROPHENYL)-4-CYANO-N-[(3S)-3,4-DIHYDROXYBUTYL]-5-(2,2-DIMETHYLPROPYL)-D-PROLINAMIDE'>I09</scene> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I09:(3R,4R,5S)-3-(3-CHLOROPHENYL)-4-(4-CHLOROPHENYL)-4-CYANO-N-[(3S)-3,4-DIHYDROXYBUTYL]-5-(2,2-DIMETHYLPROPYL)-D-PROLINAMIDE'>I09</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=4jrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jrg OCA], [https://pdbe.org/4jrg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jrg RCSB], [https://www.ebi.ac.uk/pdbsum/4jrg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jrg ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/MDM2_XENLA MDM2_XENLA] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity). | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 22: | Line 20: | ||
==See Also== | ==See Also== | ||
*[[MDM2|MDM2]] | *[[MDM2 3D structures|MDM2 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Xenopus laevis]] | ||
[[Category: | [[Category: Graves BJ]] | ||
[[Category: | [[Category: Janson CA]] | ||
[[Category: | [[Category: Lukacs C]] | ||
Revision as of 14:33, 24 November 2022
The 1.9A crystal structure of humanized Xenopus MDM2 with RO5313109 - a pyrrolidine MDM2 inhibitorThe 1.9A crystal structure of humanized Xenopus MDM2 with RO5313109 - a pyrrolidine MDM2 inhibitor
Structural highlights
FunctionMDM2_XENLA E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity). Publication Abstract from PubMedRestoration of p53 activity by inhibition of the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity. Discovery of RG7388, a Potent and Selective p53-MDM2 Inhibitor in Clinical Development.,Ding Q, Zhang Z, Liu JJ, Jiang N, Zhang J, Ross TM, Chu XJ, Bartkovitz D, Podlaski F, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B J Med Chem. 2013 Jul 16. PMID:23808545[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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