hmg coa synthase philip a. miller. sequence mevalonate pathway

HMG CoA synthase

Philip A. Miller

Sequence

Mevalonate Pathway

Overall Structural Picture

Kinetics- Difference in Rates with Mutation of Ala110Gly

Function

Electron density of the Catalytic loop

Important Amino Acids and their roles

Specific Amino Acid Integrations

Disease/Infection

• Possibility of inhibitors for Mevalonate pathway would serve great as an antibacterial specific for pathogens

• Such as Entherococcus faecalis, Streptococcus pneumoniae, and Staphylococcus aureus

• Common infections from trauma or surgical procedures• Specifically targets pathogenic bacterial, significantly more

effective than commonly used broad-spectrum antibiotics

Multiple sequence Alignment

References:• Steussy, C., Robison, A.,Tetrick, A., Knight, J., Rodwell, V.,

Stauggacher, C., Sutherlin, A., (2006) A Structural Limitation on Enzyme Activity: The Case of HMG-CoA Synthase, Biochemistry

• Stuessy, C., Vartia, A., Burgner, J., Sutherlin, A., Rodwell, V., Stauffacher, C., (2005) Biochemistry

• Sutherlin, A., Hedl, M., Sanchez-Neri, B., Burgner, J., Stauffacher, C., and Rodwell, V. (2002) Journal of Bacteriology

• Branden, Carl. Introduction to Protein Structure Garland Publishing, 1991.

• Alberts, B., Bray, D., Lewis, J., Raff, M., Roberts, K., and watson J. D. (1989) Molecular Biology of the Cell, Garland Publishing, New York