Greg Muth –Associate Professor and Chair of Chemistry Department
The bacterial enzyme Cystathionine b-lyase (CBL) catalyzes the penultimate step in the pyridoxyl 5'-phosphate (PLP) dependent hydrolysis of L-cystathionine to L-homocysteine, pyruvate and ammonia. Bacteria require L-cystathionine as a substrate in the production of methionine, an essential amino acid in protein synthesis. Because the synthesis of sulfur containing amino acids is unique to bacteria and plants, knowledge of the structure and function of enzymes involved in these pathways can lead to novel antibiotics and antifungals. There is also a strong clinical correlation between defects in the mammalian homologue, cystathionine g-lyase, and cystathiuoneuria a condition characterized by elevated homocysteine. Elevated levels of homocysteine have been correlated to cardiovascular disease, diabetes, Down's syndrome, neuroblastoma, hepatoblastoma and celaic disease. This connection makes our study of the bacterial system interesting as we apply, in principle, what we learn to a pertinent problem in current clinical biochemistry. Using a combination of functional kinetics, quaternary structure mapping and biophysical analysis we hope to unlock the mystery of how site-specific functional groups at the subunit interface contribute to the catalytic mechanism.
The project utilizes interdisciplinary techniques from biochemistry, biophysical chemistry and molecular biology.