PDBsum entry 1s3b

Oxidoreductase

PDB id: 1s3b

Contents

Protein chain

499 a.a. *

Ligands

FAD-RMA ×2

Waters ×819

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Crystal structures of monoamine oxidase b in complex with four inhibitors of the n-Propargylaminoindan class.
• Authors: C.Binda, F.Hubálek, M.Li, Y.Herzig, J.Sterling, D.E.Edmondson, A.Mattevi.
• Ref.: J Med Chem, 2004, 47, 1767-1774. [DOI no: 10.1021/jm031087c]
• PubMed id: 15027868

Abstract

Monoamine oxidase B (MAO B) is an outer mitochondrial membrane enzyme that catalyzes the oxidation of arylalkylamine neurotransmitters. The crystal structures of MAO B in complex with four of the N-propargylaminoindan class of MAO covalent inhibitors (rasagiline, N-propargyl-1(S)-aminoindan, 6-hydroxy-N-propargyl-1(R)-aminoindan, and N-methyl-N-propargyl-1(R)-aminoindan) have been determined at a resolution of better than 2.1 A. Rasagiline, 6-hydroxy-N-propargyl-1(R)-aminoindan, and N-methyl-N-propargyl-1(R)-aminoindan adopt essentially the same conformation with the extended propargyl chain covalently bound to the flavin and the indan ring located in the rear of the substrate cavity. N-Propargyl-1(S)-aminoindan binds with the indan ring in a flipped conformation with respect to the other inhibitors, which causes a slight movement of the Tyr326 side chain. Four ordered water molecules are an integral part of the active site and establish H-bond interactions to the inhibitor atoms. These structural studies may guide future drug design to improve selectivity and efficacy by introducing appropriate substituents on the rasagiline molecular scaffold.