4crt

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Crystal structure of human monoamine oxidase B in complex with the multi-target inhibitor ASS234

Structural highlights

4crt is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:ASS, FAD
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[AOFB_HUMAN] Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.

Publication Abstract from PubMed

Monoamine oxidases (MAO) and cholinesterases are validated targets in the design of drugs for the treatment of Alzheimer's disease. The multi-target compound N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methyl prop-2-yn-1-amine (ASS234), bearing the MAO-inhibiting propargyl group attached to a donepezil moiety that inhibits cholinesterases, retained activity against human acetyl- and butyryl-cholinesterases. The inhibition of MAO A and MAO B by ASS234 was characterized and compared to other known MAO inhibitors. ASS234 was almost as effective as clorgyline (kinact/KI=3x106 min-1M-1) and was shown by structural studies to form the same N5 covalent adduct with the FAD cofactor.

Kinetic and structural analysis of the irreversible inhibition of human monoamine oxidases by ASS234, a multi-target compound designed for use in Alzheimer's disease.,Esteban G, Allan J, Samadi A, Mattevi A, Unzeta M, Marco-Contelles J, Binda C, Ramsay RR Biochim Biophys Acta. 2014 Mar 16. pii: S1570-9639(14)00056-9. doi:, 10.1016/j.bbapap.2014.03.006. PMID:24642166[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
8 reviews cite this structure
Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs.
Ramsay et al. (2017)
7 more
11 other articles
No citations found

See Also

References

  1. ↑ Esteban G, Allan J, Samadi A, Mattevi A, Unzeta M, Marco-Contelles J, Binda C, Ramsay RR. Kinetic and structural analysis of the irreversible inhibition of human monoamine oxidases by ASS234, a multi-target compound designed for use in Alzheimer's disease. Biochim Biophys Acta. 2014 Mar 16. pii: S1570-9639(14)00056-9. doi:, 10.1016/j.bbapap.2014.03.006. PMID:24642166 doi:http://dx.doi.org/10.1016/j.bbapap.2014.03.006

Contents


PDB ID 4crt

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OCA

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