4U6C

HsMetAP in complex with [(1R)-1-amino-3-cyclopentylpropyl]phosphonic acid

4U6C の概要

• エントリーDOI: 10.2210/pdb4u6c/pdb
• 関連するPDBエントリー: 4U1B 4U69 4U6E 4u6j 4u6w 4u6z 4u70 4u71 4u73 4u75 4u76
• 分子名称: Methionine aminopeptidase 1, COBALT (II) ION, POTASSIUM ION, ... (6 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34910.47

構造登録者

Arya, T.,Addlagatta, A. (登録日: 2014-07-28, 公開日: 2015-03-25, 最終更新日: 2024-03-20)

主引用文献

Arya, T.,Reddi, R.,Kishor, C.,Ganji, R.J.,Bhukya, S.,Gumpena, R.,McGowan, S.,Drag, M.,Addlagatta, A.
Identification of the Molecular Basis of Inhibitor Selectivity between the Human and Streptococcal Type I Methionine Aminopeptidases
J.Med.Chem., 58:2350-2357, 2015

PubMed Abstract: The methionine aminopeptidase (MetAP) family is responsible for the cleavage of the initiator methionine from newly synthesized proteins. Currently, there are no small molecule inhibitors that show selectivity toward the bacterial MetAPs compared to the human enzyme. In our current study, we have screened 20 α-aminophosphonate derivatives and identified a molecule (compound 15) that selectively inhibits the S. pneumonia MetAP in low micromolar range but not the human enzyme. Further bioinformatics, biochemical, and structural analyses suggested that phenylalanine (F309) in the human enzyme and methionine (M205) in the S. pneumonia MetAP at the analogous position render them with different susceptibilities against the identified inhibitor. X-ray crystal structures of various inhibitors in complex with wild type and F309M enzyme further established the molecular basis for the inhibitor selectivity.

PubMed: 25699713
DOI: 10.1021/jm501790e

実験手法

X-RAY DIFFRACTION (1.91 Å)