9JEJ

Crystal structure of human EP300 KIX domain (L644C mutant)

Summary for 9JEJ

• Entry DOI: 10.2210/pdb9jej/pdb
• Descriptor: Histone acetyltransferase p300, ZINC ION (3 entities in total)
• Functional Keywords: ep300, kix domain, transcription
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 3
• Total formula weight: 36304.81

Authors

Lee, B.I.,Cho, S.E. (deposition date: 2024-09-03, release date: 2024-12-11)

Primary citation

Cho, S.E.,Lee, Y.,Kim, J.I.,Jung, K.Y.,Jeong, H.,Park, H.W.,Lee, B.I.
Comparative crystal structure analysis of the human EP300 and CBP KIX domains.
Biochem.Biophys.Res.Commun., 741:151064-151064, 2024

PubMed Abstract: Small-cell lung cancer (SCLC) is highly lethal because the tumors grow and metastasize rapidly. Effective treatments for SCLC are lacking currently. A recent study demonstrated that the E1A binding protein P300 (EP300) KIX domain has pro-tumorigenic activity and is selectively involved in the development and growth of SCLC. These findings suggest the possibility of developing small-molecule inhibitors of EP300 KIX as new targeted therapies for SCLC. In this study, we reported the crystal structure of the human EP300 KIX domain at 2.9 Å resolution except for a flexible loop and C-terminal end. The overall structure was almost identical to that of the cAMP response element-binding protein (CBP) KIX. Nine EP300 KIX residues were different from those of CBP KIX. Among these non-strictly conserved residues, Ala627, which corresponds to Asp647 in CBP KIX, reduces the negative surface potential. Asn581 and Arg613 contributed to the formation of additional hydrogen bonds in the EP300 KIX structure. Further structural analysis revealed that the hydrophobic residues that form the allosteric network in CBP KIX were well conserved in the EP300 KIX structure. This study lays the groundwork for structure-based drug design for SCLC.

PubMed: 39612645
DOI: 10.1016/j.bbrc.2024.151064

Experimental method

X-RAY DIFFRACTION (2.9 Å)