Document Detail


A key amino acid responsible for substrate selectivity of monoamine oxidase A and B.
MedLine Citation:
PMID:  9162023     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Monoamine oxidase (MAO) oxidizes biologically important amines including neurotransmitters and plays a central role in the regulation of intracellular level of these amines. Two distinct forms of MAO (MAO A and MAO B) were defined based on differences in substrate and inhibitor specificities. We earlier reported that the region between about residues 120 and 220 of rat MAO is responsible for determination of the substrate selectivity of MAO A and B (Tsugeno, Y. Hirashiki, I., Ogata, F., and Ito, A. (1995) J. Biochem. (Tokyo) 118, 974-980). To determine the essential amino acids in this region that participate in substrate recognition, a series of mutant enzymes in which amino acid residues that are conserved among various species but are different between the two forms of the enzyme were replaced with the corresponding amino acids of the counterpart and were engineered from the cDNAs of rat liver MAO A and B, and affinities for several substrates were examined. A single mutation in which Phe-208 in MAO A was substituted by the corresponding residue of Ile in MAO B was sufficient to convert the A-type substrate selectivity, and the reverse was exactly the case. Phe at this position was replaceable with Tyr for the A-type specificity and Ile was replaceable with Val and Ala for the B-type. Thus, aromatic and aliphatic residues seem to contribute to render substrate selectivity of MAO A and MAO B, respectively.
Authors:
Y Tsugeno; A Ito
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  272     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1997 May 
Date Detail:
Created Date:  1997-06-27     Completed Date:  1997-06-27     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  14033-6     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka 812-81, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Amino Acids / chemistry*,  genetics,  metabolism
Animals
Molecular Sequence Data
Monoamine Oxidase / chemistry*,  genetics,  metabolism
Point Mutation
Rats
Sequence Alignment
Substrate Specificity
Chemical
Reg. No./Substance:
0/Amino Acids; EC 1.4.3.4/Monoamine Oxidase

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