5JHU

Potent, Reversible MetAP2 Inhibitors via FBDD

5JHU の概要

• エントリーDOI: 10.2210/pdb5jhu/pdb
• 分子名称: Methionine aminopeptidase 2, MANGANESE (II) ION, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: hydrolase, peptidase, metal ion binding, proteolysis, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : P50579
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41989.45

構造登録者

Dougan, D.R. (登録日: 2016-04-21, 公開日: 2016-05-25, 最終更新日: 2024-10-16)

主引用文献

Cheruvallath, Z.,Tang, M.,McBride, C.,Komandla, M.,Miura, J.,Ton-Nu, T.,Erikson, P.,Feng, J.,Farrell, P.,Lawson, J.D.,Vanderpool, D.,Wu, Y.,Dougan, D.R.,Plonowski, A.,Holub, C.,Larson, C.
Discovery of potent, reversible MetAP2 inhibitors via fragment based drug discovery and structure based drug design-Part 1.
Bioorg.Med.Chem.Lett., 26:2774-2778, 2016

PubMed Abstract: Methionine aminopeptidase 2 (MetAP2) is an enzyme that cleaves an N-terminal methionine residue from a number of newly synthesized proteins. Pre-clinical and clinical studies suggest that MetAP2 inhibitors could be used as a novel treatment for obesity. Herein we describe our use of fragment screening methods and structural biology to quickly identify and elaborate an indazole fragment into a series of reversible MetAP2 inhibitors with <10nM potency, excellent selectivity, and favorable in vitro safety profiles.

PubMed: 27155900
DOI: 10.1016/j.bmcl.2016.04.073

実験手法

X-RAY DIFFRACTION (1.8 Å)