7uoa

MAGEA4-MTP1 linear peptide complex

spinqualitylabelsall models 7uoa, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7uoa is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.5Å Ligands: EDO, TRS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q1RN33_HUMAN Publication Abstract from PubMed MAGE proteins are cancer testis antigens (CTAs) that are characterized by highly conserved MAGE homology domains (MHDs) and are increasingly being found to play pivotal roles in promoting aggressive cancer types. MAGE-A4, in particular, increases DNA damage tolerance and chemoresistance in a variety of cancers by stabilizing the E3-ligase RAD18 and promoting trans-lesion synthesis (TLS). Inhibition of the MAGE-A4:RAD18 axis could sensitize cancer cells to chemotherapeutics like platinating agents. We use an mRNA display of thioether cyclized peptides to identify a series of potent and highly selective macrocyclic inhibitors of the MAGE-A4:RAD18 interaction. Co-crystal structure indicates that these inhibitors bind in a pocket that is conserved across MHDs but take advantage of A4-specific residues to achieve high isoform selectivity. Cumulatively, our data represent the first reported inhibitor of the MAGE-A4:RAD18 interaction and establish biochemical tools and structural insights for the future development of MAGE-A4-targeted cellular probes. Discovery and Structural Basis of the Selectivity of Potent Cyclic Peptide Inhibitors of MAGE-A4.,Fleming MC, Chiou LF, Tumbale PP, Droby GN, Lim J, Norris-Drouin JL, Williams JG, Pearce KH, Williams RS, Vaziri C, Bowers AA J Med Chem. 2022 May 26;65(10):7231-7245. doi: 10.1021/acs.jmedchem.2c00185. Epub, 2022 May 6. PMID:35522528 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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