Magister Scientiae - MSc (Medical BioSciences) / Despite attempts to develop new drugs to reduce the worldwide mortality rate attributable to
tuberculosis (TB), the illness remains a threat. Isoniazid (INH) has been used as a frontline
drug for decades. However, several resistant strains of the organism - Mycobacterium
tuberculosis (M. tuberculosis) - still emerge. The drug is mainly metabolised by a family of
enzymes, arylamine N-acetyltransferases (NAT). The three human NAT genes - NAT1,
NAT2 and the pseudogene, NATP - are found on chromosome 18p22. NAT1 and NAT2 are
isoenzymes which differ at certain amino acid positions. Subsequently, the differences affect
substrate specificity. NAT1 shows specificity to p-aminobenzoic acid (PABA) and paminosalicylate
(PAS). Previously, computer algorithms were used to predict the efficacy of
the enzyme with regard to the acetylation phenotype it confers. The two which were focused
on, Sorting Intolerant From Tolerant (SIFT) program and Polymorphism phenotyping version
2 program (PolyPhen-2), showed conflicting results for the effect of SNPs on the acetylation
rate and subsequent enzyme function. Further structural prediction methods were used to
test the effect of V231G on the structure and consequent function of the native protein,
NAT1.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uwc/oai:etd.uwc.ac.za:11394/6351 |
| Date | January 2017 |
| Creators | Willemse, Gratia-Lize |
| Contributors | Fielding, Bertrum, Christoffels, Alan |
| Publisher | University of the Western Cape |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Rights | University of the Western Cape |
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