Do monomeric vs dimeric forms of MAO-A make a difference? A direct comparison of the catalytic properties of rat and human MAO-A's.
The recent crystallographic structures of human MAO-A and rat MAO-A have shown that human MAO-A is monomeric whereas rat MAO-A is a dimer, even though they share approximately 90% sequence identity. The functional significance of this structural difference is unknown. Therefore, biochemical approaches in this paper were performed to investigate the influence of oligomeric state on functional properties of human and rat MAO-A's. The data show that 1) dimerization of MAO-A increases its structural stability; 2) the differences in kinetic properties may be caused by differences in active site structures as a result of differences in oligomeric states of the human and the rat enzymes; 3) QSAR studies show rat MAO-A as well as human MAO-A catalysis occur via proton abstraction mechanisms, and the binding of substrates is similar for both enzymes.
Wang
J
J
Department of Biochemistry and Chemistry, Emory University, Atlanta, GA 30322, USA. jwang25@emory.edu
Edmondson
D E
DE
D000818:Animals; D001596:Benzylamines / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D020134:Catalytic Domain / Q000502:physiology*; D018360:Crystallography, X-Ray; D019281:Dimerization; D004795:Enzyme Stability / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011522:Protons; D051381:Rats; D013045:Species Specificity
D001596:Benzylamines; D011522:Protons; D008995:Monoamine Oxidase