6WFK

Crystal structure of human Naa50 in complex with CoA and an inhibitor (compound 4a) identified using DNA encoded library technology

6WFK の概要

• エントリーDOI: 10.2210/pdb6wfk/pdb
• 関連するPDBエントリー: 6WF3 6WF5 6WFG
• 分子名称: N-alpha-acetyltransferase 50, COENZYME A, (4S)-1-methyl-N-{(3S,5S)-5-[4-(methylcarbamoyl)-1,3-thiazol-2-yl]-1-[4-(1H-tetrazol-5-yl)benzene-1-carbonyl]pyrrolidin-3-yl}-2,6-dioxohexahydropyrimidine-4-carboxamide, ... (4 entities in total)
• 機能のキーワード: n-alpha-acetyltransferase 50, inhibitor complex, dna encoded library, coa, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 62674.81

構造登録者

Greasley, S.E.,Feng, J.,Deng, Y.-L.,Stewart, A.E. (登録日: 2020-04-03, 公開日: 2020-07-01, 最終更新日: 2023-10-18)

主引用文献

Kung, P.P.,Bingham, P.,Burke, B.J.,Chen, Q.,Cheng, X.,Deng, Y.L.,Dou, D.,Feng, J.,Gallego, G.M.,Gehring, M.R.,Grant, S.K.,Greasley, S.,Harris, A.R.,Maegley, K.A.,Meier, J.,Meng, X.,Montano, J.L.,Morgan, B.A.,Naughton, B.S.,Palde, P.B.,Paul, T.A.,Richardson, P.,Sakata, S.,Shaginian, A.,Sonnenburg, W.K.,Subramanyam, C.,Timofeevski, S.,Wan, J.,Yan, W.,Stewart, A.E.
Characterization of SpecificN-alpha-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library.
Acs Med.Chem.Lett., 11:1175-1184, 2020

PubMed Abstract: Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded technology screening. Biophysical and biochemical data as well as cocrystal structures were obtained for both compounds ( and ) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate. Cellular target engagement experiments further confirm the Naa50 binding of and demonstrate its selectivity toward related enzymes (Naa10 and Naa60). Additional analogs of inhibitor were also evaluated to study the binding mode observed in the cocrystal structures.

PubMed: 32550998
DOI: 10.1021/acsmedchemlett.0c00029

実験手法

X-RAY DIFFRACTION (1.87 Å)