1YW9

h-MetAP2 complexed with A849519

1YW9 の概要

• エントリーDOI: 10.2210/pdb1yw9/pdb
• 関連するPDBエントリー: 1YW7 1YW8
• 分子名称: Methionine aminopeptidase 2, MANGANESE (II) ION, 2-[({2-[(1Z)-3-(DIMETHYLAMINO)PROP-1-ENYL]-4-FLUOROPHENYL}SULFONYL)AMINO]-5,6,7,8-TETRAHYDRONAPHTHALENE-1-CARBOXYLIC ACID, ... (4 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: 41912.39

構造登録者

Park, C.H. (登録日: 2005-02-17, 公開日: 2006-02-21, 最終更新日: 2011-07-13)

主引用文献

Sheppard, G.S.,Wang, J.,Kawai, M.,Fidanze, S.D.,BaMaung, N.Y.,Erickson, S.A.,Barnes, D.M.,Tedrow, J.S.,Kolaczkowski, L.,Vasudevan, A.,Park, D.C.,Wang, G.T.,Sanders, W.J.,Mantei, R.A.,Palazzo, F.,Tucker-Garcia, L.,Lou, P.,Zhang, Q.,Park, C.H.,Kim, K.H.,Petros, A.,Olejniczak, E.,Nettesheim, D.,Hajduk, P.,Henkin, J.,Lesniewski, R.,Davidsen, S.K.,Bell, R.L.
Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of albumin binding.
J.Med.Chem., 49:3832-3849, 2006

PubMed Abstract: Methionine aminopeptidase-2 (MetAP2) is a novel target for cancer therapy. As part of an effort to discover orally active reversible inhibitors of MetAP2, a series of anthranilic acid sulfonamides with micromolar affinities for human MetAP2 were identified using affinity selection by mass spectrometry (ASMS) screening. These micromolar hits were rapidly improved to nanomolar leads on the basis of insights from protein crystallography; however, the compounds displayed extensive binding to human serum albumin and had limited activity in cellular assays. Modifications based on structural information on the binding of lead compounds to both MetAP2 and domain III of albumin allowed the identification of compounds with significant improvements in both parameters, which showed good cellular activity in both proliferation and methionine processing assays.

PubMed: 16789740
DOI: 10.1021/jm0601001

実験手法

X-RAY DIFFRACTION (1.64 Å)