1O5W

The structure basis of specific recognitions for substrates and inhibitors of rat monoamine oxidase A

1O5W の概要

• エントリーDOI: 10.2210/pdb1o5w/pdb
• 分子名称: Amine oxidase [flavin-containing] A, FLAVIN-ADENINE DINUCLEOTIDE, N-[3-(2,4-DICHLOROPHENOXY)PROPYL]-N-METHYL-N-PROP-2-YNYLAMINE (3 entities in total)
• 機能のキーワード: oxidoreductase
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Mitochondrion outer membrane; Single-pass type IV membrane protein; Cytoplasmic side: P21396
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 246686.41

構造登録者

Ma, J.,Yoshimura, M.,Yamashita, E.,Nakagawa, A.,Ito, A.,Tsukihara, T. (登録日: 2003-10-06, 公開日: 2004-04-20, 最終更新日: 2024-10-23)

主引用文献

Ma, J.,Yoshimura, M.,Yamashita, E.,Nakagawa, A.,Ito, A.,Tsukihara, T.
Structure of rat monoamine oxidase a and its specific recognitions for substrates and inhibitors.
J.Mol.Biol., 338:103-114, 2004

PubMed Abstract: Monoamine oxidase (MAO), a mitochondrial outer membrane enzyme, catalyzes the degradation of neurotransmitters in the central nervous system and is the target for anti-depression drug design. Two subtypes of MAO, MAOA and MAOB, are similar in primary sequences but have unique substrate and inhibitor specificities. The structures of human MAOB complexed with various inhibitors were reported early. To understand the mechanisms of specific substrate and inhibitor recognitions of MAOA and MAOB, we have determined the crystal structure of rat MAOA complexed with the specific inhibitor, clorgyline, at 3.2A resolution. The comparison of the structures between MAOA and MAOB clearly explains the specificity of clorgyline for MAOA inhibition. The fitting of serotonin into the binding pockets of MAOs demonstrates that MAOB Tyr326 would block access of the 5-hydroxy group of serotonin into the enzyme. These results will lead to further understanding of the MAOA function and to new anti-depression drug design. This study also presents that MAOA has a transmembrane helix at the C-terminal region. This is the first crystal structure of membrane protein with an isolated transmembrane helix.

PubMed: 15050826
DOI: 10.1016/j.jmb.2004.02.032

実験手法

X-RAY DIFFRACTION (3.2 Å)