4A7A
Crystal structure of human monoamine oxidase B (MAO B) in complex with rosiglitazone
Summary for 4A7A
| Entry DOI | 10.2210/pdb4a7a/pdb |
| Related | 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 4A79 |
| Descriptor | AMINE OXIDASE [FLAVIN-CONTAINING] B, FLAVIN-ADENINE DINUCLEOTIDE, (R)-ROSIGLITAZONE, ... (4 entities in total) |
| Functional Keywords | oxidoreductase, anti-diabetes drug, parkinson's disease, neurodegeneration |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Mitochondrion outer membrane; Single-pass type IV membrane protein; Cytoplasmic side: P27338 |
| Total number of polymer chains | 2 |
| Total formula weight | 119961.41 |
| Authors | Binda, C.,Aldeco, M.,Geldenhuys, W.J.,Tortorici, M.,Mattevi, A.,Edmondson, D.E. (deposition date: 2011-11-11, release date: 2012-04-25, Last modification date: 2024-11-20) |
| Primary citation | 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 Cited by 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: 22282722DOI: 10.1021/ML200196P PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
Download full validation report
