1S2Q: Crystal Structure Of Maob In Complex With N-Propargyl-1(R)-Aminoindan (Rasagiline)

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.
PDB ID: 1S2QDownload
MMDB ID: 26988
PDB Deposition Date: 2004/1/9
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.07  Å
Source Organism:
Similar Structures:
Biological Unit for 1S2Q: dimeric; determined by author and by software (PISA)
Molecular Components in 1S2Q
Label Count Molecule
Proteins (2 molecules)
Amine Oxidase [flavin-containing] B(Gene symbol: MAOB)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB