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Dr. Nelson F.B. Phillips
Associate Professor
- Biochemistry Trainer: YES
- Phone: 216-368-4816
- Fax: 216-368-3419
- Office: W502-3
- Lab: W502
- Mail Address:
Department of Biochemistry
10900 Euclid Avenue
Cleveland, OH 44106-4935
Dr. Nelson F.B. Phillips
Our research is on pyrophosphate and polyphosphate utilizing enzymes from bacteria and protozoan parasites.
It is hypothesized that pyrophosphates (PPi) and polyphosphates (Poly P) may have served as primitive high energy compounds and during the course of evolution there may have been a transition to ATP as the phosphoryl donor. Some organisms like Giardia lamblia and Mycobacterium tuberculosis utilizes these compounds rather than ATP in certain reactions. We are investigating the structural and functional properties of two such enzymes; PPi-dependent phosphofructokinase from G. lamblia and poly P-dependent glucokinase from M. tuberculosis, using kinetics, protein chemistry and molecular biological techniques. The research is directed towards understanding the mechanisms and specific molecular structures that enable these enzymes to utilize PPi and poly P. The PPi and poly P binding sites are being characterized using chemical and affinity labels to determine if the amino acid sequences around these sites bear similarities to the ATP-binding sites of analogous enzymes from higher eukaryotes. These studies may provide evidence for the above hypothesis and the enzymes being unique to the pathogens, could be targeted for drug design.
Selected References
- Hsieh, P.-C.,et. al., and Phillips, N.F.B. Involvement of Tryptophan(s) at the active site of polyphosphate/ATP glucokinase from Mycobacterium tuberculosis. Biochemistry 32, 6243-6249 (1993).
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