My research is aimed at understanding the molecular mechanisms of biological catalysis and regulation. Mechanistic questions are probed through the study of protein and enzyme complexes with substrates, inhibitors, and transition state analogs. These types of studies have provided exciting new mechanistic information that is not accessible by other methods. Currently my research effort focuses on resolving structure-function relationships of two enzymes:
- Structure-function relationships of a unique hexameric form of the enzyme citrate synthase which is only found in gram-negative bacteria. This key metabolic enzyme is allosterically controlled via an unknown mechanism. I recently solved the complete three-dimensional structure of this enzyme and begun the process of unraveling the structure-function relationships that control its catalytic mechanism and allosteric regulation.
- Structural studies of human pancreatic alpha-amylase where the goal is to determine the nature of the catalytic mechanism of this enzyme. With this project, I obtain mechanistic insight into biological function through combined structure-function mutagenesis analyses. Controlled and systematic replacement of key functional and structural amino acids allow a truly comprehensive understanding of the roles of these individual amino acids. By combining all the available structural and functional work I then seek to expand on these studies to aid in the development of novel enzyme inhibitors and ultimately therapeutic drugs.
Structural and Mechanistic Studies of Chloride Induced Activation of Human Pancreatic Alpha-Amylase.
Maurus, R., Begum, A, Kuo, H-H, Racaza, A. , Numao, S., Anderson, C., Overall, C.W., Withers, S.G., & Brayer, G.D.
Protein Sci. 14(3):743-55. (2005)
A Novel NADH Allosteric Rgulator Site is Found on the Surface of Hexameric Type II Citrate Synthases.
Maurus, R., Nguyen, N.T., Stockell, D.J., Ayed, A., Hultin, P.G., Duckworth, H.W. & Brayer, G.D.
Biochemistry 42(19):5555-65 (2003)
Probing the Roles of Key Residues in the Unique Allosteric NADH Binding Site of Type II Citrate Synthase of E. coli.
Stokell, D.J., Donald, L.J., Maurus, R., Nguyen, N.T., Sadler, G., Choudhary, K., Hultin, P.G., Brayer, G.D, & Duckworth, H.W.
J. Biol. Chem. 278(37):35435-43 (2003)
Introduction and Characterization of a Functionally-Linked Metal Ion Binding Site at the Exposed Heme Edge of Myoglobin.
Hunter, C.L., Maurus, R., Mauk, M.R. Lee, H., Ferrer, J.C., Tong, H., Nguyen, N.T., Smith, M., Baryer, G.D. & Mauk, G.
Proc. Natl. Acad. Sci. U.S.A. 100(7):3647-52. (2003)
Mechanistic Analyses of Catalysis in Human Pancreatic Alpha-Amylase: Detailed Kinetic and Structural Studies of Mutants of Three Conserved Carboxylic Acids.
E.H. Rydberg, C. Li, R. Maurus, C.M. Overall, G.D. Brayer and S.G. Withers
Biochemistry 41(13), 4492-502 (2002)
Probing the Role of the Chloride Ion in the Mechanism of Human Pancreatic Alpha-Amylase.
S. Numao, R. Maurus, G. Sidhu, Y. Wang, C.M. Overall, G.D. Brayer and S.G. Withers
Biochemistry 41(1), 215-25 (2002)
Comparative Analysis of Folding and Substrate Binding Sites Between Regulated Hexameric Type II Citrate Synthases and Unregulated Dimeric Type I Enzymes.
N.T. Nguyen, R. Maurus, D.J. Stokell, A. Ayed, H.T. Duckworth and Brayer G.D.
Biochemistry 40(44), 13177-87 (2001)
Subsite Mapping of the Human Pancreatic alpha-Amylase Active Site Through Structural, Kinetic and Mutagenesis.
G.D. Brayer, S. Sidhu, R. Maurus, C. Braun, Y. Wang, N.T. Nguyen, C.M. Overall and S.G. Withers
Biochemistry 39(16), 4778-91 (2000)
Structural and Spectroscopic Studies of Azide Complexes of Horse Heart Myoglobin and the His-64-Thr Variant.
R. Maurus, R. Bogumil, N.T. Nguyen, A.G. Mauk and G. Brayer
Biochemical Journal. 332, 67-74 (1998)
Thermal Destabilization of Horse Heart Myoglobin Through Modification of a Hydrophobic Cluster in the Proximal Heme Pocket.
R. Maurus, C.M. Overall, R. Bogumil, Y. Luo, A.G. Mauk, M. Smith and G.D. Brayer
Biochim. Biophys. Acta, Protein Structure and Molecular Enzymology 1341(1), 1-13 (1995)
Electrostatic Modification of the Active Site of Myoglobin: Characterization of the Proximal Ser92Asp Variant.
E. Lloyd, D.L. Burk, J.C. Ferrer, R. Maurus, J. Doran, P.R. Carey, G.D. Brayer and A.G. Mauk
Biochemistry 35, 11901-12 (1996)
Origin of the pH-Dependent Spectroscopic Properties of Pentacoordinate Metmyoglobin Variants.
R. Bogumil, R. Maurus, D.P. Hildebrand, G.D. Brayer and A.G. Mauk
Biochemistry 34, 10483-10490 (1995)
The Proximal Ligand Variant His93Tyr of Horse Heart Myoglobin.
D.P. Hildebrand, D.L. Burk, R. Maurus, J.C. Ferrer, G.D. Brayer and A.G. Mauk
Biochemistry 34, 1997-2005 (1995)
Structural Characterization of Heme Ligation in the His64Tyr Variant of Myoglobin.
R. Maurus, R. Bogumil, Y. Luo, H-T. Tang, M. Smith, A.G. Mauk and G.D. Brayer
J. Biol. Chem. 269, 12606-12610 (1994)
FTIR Analysis of the Interaction of Azide with Horse Heart Myoglobin Variants.
R. Bogumil, C.L. Hunter, R. Maurus, H-T. Tang, H. Lee, E. Lloyd, G.D. Brayer, M. Smith and A.G. Mauk
Biochemistry 33, 7600-7608 (1994)