Increased Enzyme Flexibility Doesnot Necessarily Lead to Substrate Promiscuity

Understanding the molecular basis of substrate promiscuity shown by some enzymes has been quite elusive. Enzymes that catalyze modification of aminoglycoside antibiotics show a wide range of substrate promiscuity.

Comparisons based on amino acid sequence similarity have been more confusing than leading to any explanations.

For example, several aminoglycoside modifying enzymes that catalyze different reactions and have less than 5% sequence identity and less than 12% sequence similarity show high overlap in their substrate profiles while some others despite catalyzing the same reaction and having >50% sequence similarity can have significant differences in their substrate profiles

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