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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