8Q23 の概要
| エントリーDOI | 10.2210/pdb8q23/pdb |
| 分子名称 | Glycylpeptide N-tetradecanoyltransferase 1, ACE-ORD-SER-PHE-SER-LYS-PRO-ARG, GLYCEROL, ... (6 entities in total) |
| 機能のキーワード | e-myristoylation, nmt, myristoyltransferase type1, acyltransferase, gnat, gcn5-related n-acetyltransferases, transferase |
| 由来する生物種 | Homo sapiens (human) 詳細 |
| タンパク質・核酸の鎖数 | 4 |
| 化学式量合計 | 97108.56 |
| 構造登録者 | |
| 主引用文献 | Riviere, F.,Dian, C.,Dutheil, R.F.,Monassa, P.,Giglione, C.,Meinnel, T. Novel, tightly structurally related N-myristoyltransferase inhibitors display equally potent yet distinct inhibitory mechanisms. Structure, 32:1737-1750.e3, 2024 Cited by PubMed Abstract: N-myristoyltransferases (NMTs) catalyze essential acylations of N-terminal alpha or epsilon amino groups of glycines or lysines. Here, we reveal that peptides tightly fitting the optimal glycine recognition pattern of human NMTs are potent prodrugs relying on a single-turnover mechanism. Sequence scanning of the inhibitory potency of the series closely reflects NMT glycine substrate specificity rules, with the lead inhibitor blocking myristoylation by NMTs of various species. We further redesigned the series based on the recently recognized lysine-myristoylation mechanism by taking advantage of (1) the optimal peptide chassis and (2) lysine side chain mimicry with unnatural enantiomers. Unlike the lead series, the inhibitory properties of the new compounds rely on the protonated state of the side chain amine, which stabilizes a salt bridge with the catalytic base at the active site. Our study provides the basis for designing first-in-class NMT inhibitors tailored for infectious diseases and alternative active site targeting. PubMed: 39208793DOI: 10.1016/j.str.2024.08.001 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (1.9 Å) |
構造検証レポート
検証レポート(詳細版)
をダウンロード
をダウンロード
