{'fraction_non_alphanumeric': 0.024475524475524476, 'fraction_numerical': 0.046153846153846156, 'mean_word_length': 5.012605042016807, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Phe208 and Ile199 in Human Monoamine Oxidase A and B Do Not Determine Substrate and Inhibitor Specificities as in Rat

Abstract: It has been reported previously that reciprocally switching Phe208 and Ile199 in rat monoamine oxidase (MAO) A and B, respectively, was sufficient to switch their substrate and inhibitor preferences. In this study, the same mutants were made in the human forms of MAO. When compared with MAO A, MAO A‐F208I showed a sixfold decrease in the specificity constant kcat/Km for both the MAO A‐ and the MAO B‐preferring substrates 5‐hydroxytryptamine and β‐phenylethylamine, respectively. The reciprocal point mutant MAO B‐I199F had no effect on substrate affinity. To investigate if the region neighboring these two residues is responsible for conferring preferences, we have also made chimeric constructs by reciprocally switching the corresponding amino acid segments 159‐214 in MAO A and 150‐205 in MAO B. Chimerics MAO AB159‐214A and MAO BA150‐205B had small changes in Km and IC50 values when compared with MAO A and B, respectively, but did not exhibit a preference switch. The results suggest that Phe208 in MAO A and amino acid segments 159‐214 and 150‐205 in MAO A and B, respectively, influence the enzyme active site. However, substrate and inhibitor preferences of human MAO A and B are not determined by the respective residues Phe108 and Ile199 as in rat MAO nor by their neighboring regions.