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.
3tu1
From Proteopedia
Exhaustive Fluorine Scanning towards Potent p53-MDM2 Antagonist
Structural highlights
DiseaseMDM2_HUMAN Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding. FunctionMDM2_HUMAN E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] Publication Abstract from PubMedFluorine dance: We discovered potent p53-Mdm2 antagonists by systematically varying the fluorine substitution pattern around a benzyl group that undergoes stacking interactions with His 96 of Mdm2. The potency of the optimized enantiomer (S)-7 e is >50-fold better than the worst compound of the series. All compounds were efficiently synthesized by Ugi multicomponent reaction chemistry. Exhaustive Fluorine Scanning toward Potent p53-Mdm2 Antagonists.,Huang Y, Wolf S, Koes D, Popowicz GM, Camacho CJ, Holak TA, Domling A ChemMedChem. 2012 Jan 2;7(1):49-52. doi: 10.1002/cmdc.201100428. Epub 2011, Sep 27. PMID:21954050[12] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
Categories: Homo sapiens | Large Structures | Camacho CJ | Doemling A | Holak TA | Huang Y | Koes D | Popowicz GM | Wolf S
