4IKS

Crystal structure of truncated (delta 1-89) human methionine aminopeptidase Type 1 in complex with N1-(5-chloro-6-methyl-2-(pyridin-2-yl)pyrimidin-4-yl)-N2-(6-(trifluoromethyl)pyridin-2-yl)ethane-1,2-diamine

4IKS の概要

• エントリーDOI: 10.2210/pdb4iks/pdb
• 関連するPDBエントリー: 4IKR 4IKT 4IKU
• 分子名称: Methionine aminopeptidase 1, N-[5-chloro-6-methyl-2-(pyridin-2-yl)pyrimidin-4-yl]-N'-[6-(trifluoromethyl)pyridin-2-yl]ethane-1,2-diamine, COBALT (II) ION, ... (6 entities in total)
• 機能のキーワード: pita-bread fold, aminopeptidase, ribosome, 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: 37652.72

構造登録者

Addlagatta, A.,Kishor, C.,Arya, T. (登録日: 2012-12-28, 公開日: 2013-12-11, 最終更新日: 2024-03-20)

主引用文献

Kishor, C.,Arya, T.,Reddi, R.,Chen, X.,Saddanapu, V.,Marapaka, A.K.,Gumpena, R.,Ma, D.,Liu, J.O.,Addlagatta, A.
Identification, Biochemical and Structural Evaluation of Species-Specific Inhibitors against Type I Methionine Aminopeptidases
J.Med.Chem., 56:5295-5305, 2013

PubMed Abstract: Methionine aminopeptidases (MetAPs) are essential enzymes that make them good drug targets in cancer and microbial infections. MetAPs remove the initiator methionine from newly synthesized peptides in every living cell. MetAPs are broadly divided into type I and type II classes. Both prokaryotes and eukaryotes contain type I MetAPs, while eukaryotes have additional type II MetAP enzyme. Although several inhibitors have been reported against type I enzymes, subclass specificity is scarce. Here, using the fine differences in the entrance of the active sites of MetAPs from Mycobacterium tuberculosis , Enterococcus faecalis , and human, three hotspots have been identified and pyridinylpyrimidine-based molecules were selected from a commercial source to target these hotspots. In the biochemical evaluation, many of the 38 compounds displayed differential behavior against these three enzymes. Crystal structures of four selected inhibitors in complex with human MetAP1b and molecular modeling studies provided the basis for the binding specificity.

PubMed: 23767698
DOI: 10.1021/jm400395p

実験手法

X-RAY DIFFRACTION (1.7 Å)