title: Examining electrostatic preorganization in monoamine oxidases A and B by structural comparison and pKa calculations.
abstract: Monoamine oxidases (MAO) A and B are important flavoenzymes involved in the metabolism of amine neurotransmitters. Orru et al. ( J. Neural Transm. 2013 , 120 , 847 - 851 ) recently presented experimental results that have challenged the prevailing assumption that MAO A and MAO B employ an identical catalytic mechanism. We compared the spatial configuration of ionizable groups in both isozymes and estimated the time-averaged electrostatic potential by calculating the pKa values of five active site residues. Superimposition of both experimental structures shows very close overlap and the RMSD in placements of ionizable groups within 16 Å of the reaction center is only 0.847 Å. This similarity is also reflected in the calculated pKa values, where the largest difference between the MAO A and MAO B pKa values was found for residues Tyr188 in MAO B and the corresponding Tyr197 in MAO A assuming 1.23 units. The pKa values for the other four studied residues differ by less than 0.75 units. The results show that the electrostatic preorganizations in both active sites are very similar, supporting the idea that both enzymes work by the same mechanism.
authors.affiliation: Laboratory for Biocomputing and Bioinformatics, National Institute of Chemistry , Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
authors.forename: Matej
authors.initials: M
authors.lastname: Repič
authors.forename: Miha
authors.initials: M
authors.lastname: Purg
authors.forename: Robert
authors.initials: R
authors.lastname: Vianello
authors.forename: Janez
authors.initials: J
authors.lastname: Mavri
mesh_terms: D020134:Catalytic Domain; D004298:Dopamine / Q000737:chemistry; D007527:Isoenzymes / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000737:chemistry*; D055672:Static Electricity; D014443:Tyrosine / Q000737:chemistry
chemical_list: D007527:Isoenzymes; D014443:Tyrosine; D008995:Monoamine Oxidase; D004298:Dopamine