4PNC

E. COLI METHIONINE AMINOPEPTIDASE IN COMPLEX WITH INHIBITOR 7-METHOXY-2-METHYLEN-3,4-DIHYDRONAPHTHALEN-1(2H)-ONE

4PNC の概要

• エントリーDOI: 10.2210/pdb4pnc/pdb
• 関連するPDBエントリー: 1XNZ 1YVM 3MAT
• 分子名称: Methionine aminopeptidase, (2S)-7-methoxy-2-methyl-3,4-dihydronaphthalen-1(2H)-one, COBALT (II) ION, ... (5 entities in total)
• 機能のキーワード: hydrolase(alpha-aminoacylpeptide), metal complex, methionine aminopeptidase, covalent inhibitor, 1-tetralone, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29731.80

構造登録者

Scheidig, A.J.,Altmeyer, M.,Klein, C.D. (登録日: 2014-05-23, 公開日: 2014-07-23, 最終更新日: 2024-11-20)

主引用文献

Altmeyer, M.,Amtmann, E.,Heyl, C.,Marschner, A.,Scheidig, A.J.,Klein, C.D.
Beta-aminoketones as prodrugs for selective irreversible inhibitors of type-1 methionine aminopeptidases.
Bioorg.Med.Chem.Lett., 24:5310-5314, 2014

PubMed Abstract: We identified and characterized β-aminoketones as prodrugs for irreversible MetAP inhibitors that are selective for the MetAP-1 subtype. β-Aminoketones with certain structural features form α,β-unsaturated ketones under physiological conditions, which bind covalently and selectively to cysteines in the S1 pocket of MetAP-1. The binding mode was confirmed by X-ray crystallography and assays with the MetAPs from Escherichia coli, Staphylococcus aureus and both human isoforms. The initially identified tetralone derivatives showed complete selectivity for E. coli MetAP versus human MetAP-1 and MetAP-2. Rational design of indanone analogs yielded compounds with selectivity for the human type-1 versus the human type-2 MetAP.

PubMed: 25293447
DOI: 10.1016/j.bmcl.2014.09.047

実験手法

X-RAY DIFFRACTION (1.54 Å)