1M4H

Crystal Structure of Beta-secretase complexed with Inhibitor OM00-3

1M4H の概要

• エントリーDOI: 10.2210/pdb1m4h/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000289
• 分子名称: beta-Secretase, Inhibitor OM00-3 (3 entities in total)
• 機能のキーワード: memapsin2, base, asp2, alzheimer's disease, aspartic protease, acid protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P56817
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 89126.50

構造登録者

Hong, L.,Turner, R.T.,Koelsch, G.,Ghosh, A.K.,Tang, J. (登録日: 2002-07-02, 公開日: 2002-08-28, 最終更新日: 2024-11-20)

主引用文献

Hong, L.,Turner, R.T.,Koelsch, G.,Shin, D.,Ghosh, A.K.,Tang, J.
Crystal Structure of Memapsin 2 (beta-Secretase) in Complex with Inhibitor OM00-3
Biochemistry, 41:10963-10967, 2002

PubMed Abstract: The structure of the catalytic domain of human memapsin 2 bound to an inhibitor OM00-3 (Glu-Leu-Asp-LeuAla-Val-Glu-Phe, K(i) = 0.3 nM, the asterisk denotes the hydroxyethylene transition-state isostere) has been determined at 2.1 A resolution. Uniquely defined in the structure are the locations of S(3)' and S(4)' subsites, which were not identified in the previous structure of memapsin 2 in complex with the inhibitor OM99-2 (Glu-Val-Asn-LeuAla-Ala-Glu-Phe, K(i) = 1 nM). Different binding modes for the P(2) and P(4) side chains are also observed. These new structural elements are useful for the design of new inhibitors. The structural and kinetic data indicate that the replacement of the P(2)' alanine in OM99-2 with a valine in OM00-3 stabilizes the binding of P(3)' and P(4)'.

PubMed: 12206667
DOI: 10.1021/bi026232n

実験手法

X-RAY DIFFRACTION (2.1 Å)