The FAD binding sites of human monoamine oxidases A and B.

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Edmondson DE, Binda C, Mattevi A

The FAD binding sites of human monoamine oxidases A and B.

Neurotoxicology. 2004 Jan;25(1-2):63-72. doi: 10.1016/S0161-813X(03)00114-1.

PubMed ID

14697881 [ View in PubMed

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Abstract

The structural details of the interactions of the covalent 8alpha-S-cysteinyl-FAD with the protein moiety in monoamine oxidase B (MAO B) based on the MAO B crystal structure are described. The dinucleotide is bound to the protein in an extended conformation with the majority of the bonds to the protein identified as hydrogen bonds with amino acid side chains, amide bonds, and water molecules. Since those amino acids interacting with the FAD are conserved in monoamine oxidase A (MAO A), it is proposed that the FAD binding site in MAO A is quite similar to that in MAO B. The redox-active isoalloxazine ring is buried in the protein without direct access to bulk solvent. An electrostatic interaction is observed between the anionic pyrophosphate moiety and Arg42. The normally flat oxidized flavin ring is in a bent, puckered conformation in the MAO B binding site which is suggested to contribute to its reactivity in catalysis. This structural information is then used to explain previous studies on flavin analog incorporation into either MAO B or into MAO A.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Flavin adenine dinucleotide	Amine oxidase [flavin-containing] B	Protein	Humans	Unknown	Not Available	Details