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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts
89
18-POS
Board 18
Substrate Specificity in the Amidases of Biomedical Importance – Insights from the Crystal
Structures of a Model Bacterial Amidase
S. W. Kimani
, B T. Sewell.
University of Cape Town, Cape Town, South Africa.
S.W Kimani is the Wirsam Scholar
Nitrilase superfamily amidases predominantly catalyze the conversion of amides to their
corresponding acids and ammonia, with only a small subset performing the reverse amidase
activity of condensation of non-peptidic amide bonds. These enzymes perform diverse but
essential metabolic roles in vivo including detoxification of small molecules, protein post-
translational modifications, protein degradation, and vitamin and co-enzyme biosynthesis, among
others. Of importance are the medically-relevant amidases like the NAD+ synthetase and
apolipoprotein N-acyltransferases from Mycobacterium tuberculosis and other pathogenic
organisms, which play critical roles in NAD+ cofactor homeostasis and biosynthesis of mature
membrane triacylated lipoproteins respectively, and have therefore been considered as potential
targets for inhibitor design. Very little is however known about substrate specificity and catalysis
in these enzymes. Using active site mutants of a model amidase from Nesterenkonia species, we
have been able to understand how amidases recognize and bind amide substrates, as well as the
contribution of the active site pocket size and geometry to substrate specificity and catalysis.
Findings from this work will be presented. Dr Kimani’s participation has been made possible by
WIRSAM SCIENTIFIC, agents for Rigaku.