1s3b
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(New page: 200px<br /> <applet load="1s3b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s3b, resolution 1.65Å" /> '''Crystal structure o...)
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Revision as of 17:03, 12 November 2007
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Crystal structure of MAOB in complex with N-methyl-N-propargyl-1(R)-aminoindan
Overview
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.
About this Structure
1S3B is a Single protein structure of sequence from Homo sapiens with FAD as ligand. Active as Amine oxidase (flavin-containing), with EC number 1.4.3.4 Full crystallographic information is available from OCA.
Reference
Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class., Binda C, Hubalek F, Li M, Herzig Y, Sterling J, Edmondson DE, Mattevi A, J Med Chem. 2004 Mar 25;47(7):1767-74. PMID:15027868
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