4A79

Crystal structure of human monoamine oxidase B (MAO B) in complex with pioglitazone

4A79 の概要

• エントリーDOI: 10.2210/pdb4a79/pdb
• 関連するPDBエントリー: 1GOS 1H8R 1OJ9 1OJA 1OJC 1OJD 1S2Q 1S2Y 1S3B 1S3E 2BK3 2BK4 2BK5 2BYB 2C64 2C65 2C66 2C67 2C70 2C72 2C73 2C75 2C76 2V5Z 2V60 2V61 2VRL 2VRM 2VZ2 2XCG 2XFN 2XFO 2XFP 2XFQ 2XFU 3ZYX 4A7A
• 分子名称: AMINE OXIDASE [FLAVIN-CONTAINING] B, FLAVIN-ADENINE DINUCLEOTIDE, (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, anti-diabetes drug, parkinson's disease, neurodegeneration
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Mitochondrion outer membrane; Single-pass type IV membrane protein; Cytoplasmic side: P27338
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 119959.44

構造登録者

Binda, C.,Aldeco, M.,Geldenhuys, W.J.,Tortorici, M.,Mattevi, A.,Edmondson, D.E. (登録日: 2011-11-11, 公開日: 2012-04-25, 最終更新日: 2024-10-23)

主引用文献

Binda, C.,Aldeco, M.,Geldenhuys, W.J.,Tortorici, M.,Mattevi, A.,Edmondson, D.E.
Molecular Insights Into Human Monoamine Oxidase B Inhibition by the Glitazone Anti-Diabetes Drugs
Acs Med. Chem. Lett., 3:39-42-, 2012

PubMed Abstract: The widely employed anti-diabetic drug pioglitazone (Actos) is shown to be a specific and reversible inhibitor of human monoamine oxidase B (MAO B). The crystal structure of the enzyme-inhibitor complex shows the R-enantiomer is bound with the thiazolidinedione ring near the flavin. The molecule occupies both substrate and entrance cavities of the active site establishing non-covalent interactions with the surrounding amino acids. These binding properties differentiate pioglitazone from the clinically used MAO inhibitors, which act through covalent inhibition mechanisms and do not exhibit a high degree of MAO A versus B selectivity. Rosiglitazone (Avandia) and troglitazone, other members of the glitazone class, are less selective in that they are weaker inhibitors of both MAO A and MAO B These results suggest that pioglitazone may have utility as a "re-purposed" neuro-protectant drug in retarding the progression of disease in Parkinson's patients. They also provide new insights for the development of reversible isoenzyme-specific MAO inhibitors.

PubMed: 22282722
DOI: 10.1021/ML200196P

実験手法

X-RAY DIFFRACTION (1.89 Å)