The Impact of double mutant residues E57D/E219Q and E57Q/E219Q on M.tuberculosis indole-3-glycerol phosphate synthase catalysis
Presentation Type
Poster
Faculty Advisor
Nina Goodey
Access Type
Event
Start Date
26-4-2023 1:44 PM
End Date
26-4-2023 2:45 PM
Description
Tuberculosis (TB) is a progressive infectious disease mostly caused by Mycobacterium tuberculosis and that primarily affects the lungs. Tuberculosis remains the leading cause of death from an infectious disease among adults worldwide, with more than 10 million people becoming newly sick from tuberculosis each year. There is a high increase in drug resistance for tuberculosis, paving a way for new drug targets to be developed. The potential drug target chosen is the enzyme Indole-3-glycerol phosphate synthase (MtIGPS), which plays an important role in tryptophan biosynthesis and catalyzes the conversion of 1-(o-carboxyphenylamino)-1-deoxyribulose 5’-phosphate (CdRP) into indole-glycerol-phosphate (IGP) in the bacterial tryptophan biosynthetic pathway. The introduction of mutations to residues that play an important role in catalysis or binding between the ligands and MtIGPS can provide information about the roles of these residues. The two mutants E57D/E219Q and E57Q/E219Q were expressed, purified and their catalytic activities were measured. A kcat value of 4.89× 10-5 1/s for E57D/E219Q, 2.13× 10-5 1/s for E57Q/E219Q and 7.4× 10-2 1/s for the wild type were obtained. These data Indicate that residues E57D and E219Q on MtIGPS are catalytically important due to the amount of CdRP converted per unit time shown from the kcat values.
The Impact of double mutant residues E57D/E219Q and E57Q/E219Q on M.tuberculosis indole-3-glycerol phosphate synthase catalysis
Tuberculosis (TB) is a progressive infectious disease mostly caused by Mycobacterium tuberculosis and that primarily affects the lungs. Tuberculosis remains the leading cause of death from an infectious disease among adults worldwide, with more than 10 million people becoming newly sick from tuberculosis each year. There is a high increase in drug resistance for tuberculosis, paving a way for new drug targets to be developed. The potential drug target chosen is the enzyme Indole-3-glycerol phosphate synthase (MtIGPS), which plays an important role in tryptophan biosynthesis and catalyzes the conversion of 1-(o-carboxyphenylamino)-1-deoxyribulose 5’-phosphate (CdRP) into indole-glycerol-phosphate (IGP) in the bacterial tryptophan biosynthetic pathway. The introduction of mutations to residues that play an important role in catalysis or binding between the ligands and MtIGPS can provide information about the roles of these residues. The two mutants E57D/E219Q and E57Q/E219Q were expressed, purified and their catalytic activities were measured. A kcat value of 4.89× 10-5 1/s for E57D/E219Q, 2.13× 10-5 1/s for E57Q/E219Q and 7.4× 10-2 1/s for the wild type were obtained. These data Indicate that residues E57D and E219Q on MtIGPS are catalytically important due to the amount of CdRP converted per unit time shown from the kcat values.