Examining electrostatic preorganization in monoamine oxidases A and B by structural comparison and pKa calculations (CROSBI ID 206348)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Repič, Matej ; Purg, Miha ; Vianello, Robert ; Mavri, Janez
engleski
Examining electrostatic preorganization in monoamine oxidases A and B by structural comparison and pKa calculations
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.
monoamine oxidase
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Podaci o izdanju
118 (16)
2014.
4326-4332
objavljeno
1520-6106
10.1021/jp500795p