Grover L. Waldrop
Associate Professor
BS: Syracuse University,1981
MS: State University of New York, Buffalo, 1983
PhD: State University of New York, Buffalo, 1988
Phone: (225) 578-5209
E-mail: gwaldro@lsu.edu
Office: 206 Life Sciences Building
Area of Interest
General Area: Kinetic and Chemical Mechanisms of Enzymes
Since arriving at LSU the research efforts in the laboratory have focused primarily on acetyl CoA carboxylase (ACCase). ACCase catalyzes the committed and regulated step in fatty acid synthesis in all animals, plants and bacteria. This enzyme is a target for antibiotics, herbicides and anti-obesity agents. For the past 7 years, part of our effort has 1 of 12 involved collaborating with Pfizer to develop the bacterial form of the enzyme as a new target for antibiotics. To study the structure and function of ACCase we use a variety of mechanistic techniques including steady-state and rapid reaction kinetics, inhibitor design, isotope effects and site-directed mutagenesis. Structural analyses are carried out by x-ray crystallography.
The basic research I have done for the last 14 years has recently led to several new research activities with a more applied focus.
Academic Drug Design. Leveraging knowledge from the Pfizer collaboration to develop new antibiotics to treat TB (a neglected tropical disease).
Collaboration with Faculty from Mechanical Engineering to use ACCase as an enzymatic molecular machine (i.e. nanotechnology).
Collaboration with scientists from the Audubon Sugar Institute at LSU to isolate and characterize lignocellulosic degrading enzymes for use in ethanol production.
Awards & Honors
Damon Runyon-Walter Winchell Cancer Research Fund Fellowship, University of California-Berkeley, 9/88-8/91
Beginning Investigator Award from the American Heart Association, University of Wisconsin-Madison, 7/94-8/95
LSU Tiger Athletic Foundation Excellence in Undergraduate Teaching Award, 2004.
Beginning Investigator Award from the American Heart Association, University of Wisconsin-Madison, 7/94-8/95
LSU Tiger Athletic Foundation Excellence in Undergraduate Teaching Award, 2004.
Selected Publications
Kinetic Mechanism and Structural Requirements of the Amine-Catalyzed Decarboxylation of Oxaloacetic Acid. Thalji, N.K., Crowe, W.E. and Waldrop, G.L. (2009). J. Org. Chem. 74, 144-152.
Umbrella Sampling Simulations of Biotin Carboxylase: Is a Structure with an Open ATP Grasp Domain Stable in Solution? Novak, B.R., Moldovan, D., Waldrop, G.L. and de Queiroz, M.S. (2009). J. Phys. Chem., in press.
The Utility of Molecular Dynamics Simulations for Understanding Site-Directed Mutagenesis of Glycine Residues in Biotin Carboxylase. Bordelon, T., Nilsson Lill, S.O., and Waldrop, G.L. (2009). Proteins: Struct. Funct. Bioinf. 74, 808-819.
Structural Evidence for Substrate-Induced Synergism and Half-Sites Reactivity in Biotin Carboxylase. Mochalkin, I., Miller, J.R., Evdokimov, A., Lightle, S., Yan, C., Stover, C.K. and Waldrop, G.L. (2008). Protein Sci, 17, 1706-1718.
Molecular Dynamics Simulations of Biotin Carboxylase. Nilsson Lill, S.O., Gao, J. and Waldrop, G.L. (2008). J. Phys. Chem. B 112, 3149-3156.
DNA Inhibits Catalysis by the Carboxyltransferase Subunit of Acetyl-CoA Carboxylase: Implications for Active Site Communication. Benson, B. K., Meades, G., Jr., Grove, A., Waldrop, G.L. (2008). Prot. Sci. 17, 34-42. 2 of 12
Modeling and Numerical Simulation of Biotin Carboxylase Kinetics: Implications for Half-Sites Reactivity. de Queiroz, M.S. and Waldrop, G.L. (2007) J. Theor. Biol. 246, 167-175.
The Structure of the Carboxyltransferase Component of Acetyl-CoA Carboxylase Reveals a Zinc-binding Motif Unique to the Bacterial Enzyme. Bilder, P., Lightle, S., Bainbridge, G., Jeffrey Ohren, Barry Finzel, Fang Sun, Susan Holley, Loola Al- Kassim, Cindy Spessard, Michael Melnick, Marcia Newcomer and Waldrop,G.L. (2006) Biochemistry 279, 15772-15778.
A High Throughput Screening Assay for the Carboxyltransferase Subunit of Acetyl-CoA Carboxylase. Santoro, N., Brtva, T., Vander Roest, S., Siegel, K. and Waldrop,G.L. (2006) Analytical Biochemistry 354, 70-77.
A Novel Slow-Tight Binding Serine Protease Inhibitor from Eastern Oyster (Crassostrea virginca) plasmas Inhibits Perkinsin, the Major Extracellular Protease of the Oyster Protozoan Parasite Perkinsus marinus. Xue, Q., Waldrop, G.L., Schey, K.L., Itoh, N., Ogawa, M. Cooper, R.K., Losso, J.N., La Peyre, J. (2006) Comp. Biochem. Physiol., Part.B 145, 16-26.
The regulatory role of residues 226-232 in phosphoenolpyruvate carboxylase from maize. Yuan, J., Sayegh, J., Mendez, J., Sward, L., Sanchez, N., Sanchez, S., Waldrop, G.L. and Grover, S. (2006) Photosyn. Res. 88, 73-81.
Kinetic Characterization of Mutations found in Propionic Acidemia and Methylcrotonylglycinuria: Evidence for Cooperativity in Biotin Carboxylase. Sloane, V. and Waldrop,G.L. (2004). J. Biol. Chem. 279, 15772-15778.
Targeting Acetyl-CoA Carboxylase for Anti-Obesity Therapy. Waldrop, G.L. and Stephens, J.M. (2003). Current Med. Chem. 3, 229-234.
Multi-subunit Acetyl-CoA Carboxylases. Cronan, J.E. and Waldrop, G.L. (2002). Prog. Lipid Res. 41, 407-435.
A Biotin Analog Inhibits Acetyl-CoA Carboxylase Activity and Adipogenesis. Levert, K.L., Waldrop, G.L. and Stephens, J.M. (2002). J. Biol. Chem. 277, 16347-16350.
A Bisubstrate Analog Inhibitor of the Carboxyltransferase Component of Acetyl- CoA Carboxylase. Levert, K.L. and Waldrop, G.L. (2002). Biochem. Biophys. Res. Comm. 291, 1213-1217.
Site-Directed Mutagenesis of ATP Binding Residues of Biotin Carboxylase: Insight into the Mechanism of Catalysis. Sloane, V., Blanchard, C.Z., Guillot, F. and Waldrop, G.L. (2001). J. Biol. Chem. 276, 24991-24996. 3 of 12
Function of Escherichia coli Biotin Carboxylase Requires Catalytic Activity of Both Subunits of the Homodimer. Janiyani, K., Bordelon, T., Waldrop, G.L. and Cronan, J.E. (2001). J. Biol. Chem. 276, 29864-29870.
Benzyl, 5-(2-[2-(diethoxyphosphinoyl)acetyl]-3-oxo-7-thia-2,4- diazadicyclo[3.3.0]oct-6-yl)pentanoate, a novel biotin derivative. Amspacher, D.R., Blanchard, C.Z., Saraiva, M.C., Waldrop, G.L., Strongin, R.M. and Fronczek, F.R. (2000) Acta Crystallographica, Section C 56, E305-E306.
Do Cysteine 230 and Lysine 238 of Biotin Carboxylase Play a Role in the Activation of Biotin? Levert, K.L., Lloyd, R.B. and Waldrop, G.L. (2000). Biochemistry 39, 4122-4128.
Movement of the Biotin Carboxylase B-Domain as a Result of ATP-Binding. Thoden, J.B., Blanchard, C.Z., Holden, H.M. and Waldrop, G.L. (2000). J. Biol. Chem. 275, 16183-16190.
Mutations at Four Active Site Residues of Biotin Carboxylase Abolish Substrate- Induced Synergism by Biotin. Blanchard, C.Z., Lee, Y.M., Frantom, P.A. and Waldrop, G.L. (1999). Biochemistry, 38, 3393-3400.
Synthesis of a Reaction Intermediate Analogue of Biotin-Dependent Carboxylases via a Selective Derivatization of Biotin. Amspacher, D.R., Blanchard, C.Z., Fronczek, F.R., Saraiva, M.C., Waldrop, G.L. and Strongin, R.M. (1999). Organic Lett. 1, 99-102.
The Biotin Domain Peptide from the Biotin Carboxyl Carrier Protein of Escherichia coli Acetyl-CoA Carboxylase Causes a Marked Increase in the Catalytic Efficiency of Biotin Carboxylase and Carboxyltransferase Relative to Free Biotin. Blanchard, C.Z., Chapman-Smith, A., Wallace, J.C. and Waldrop, G.L. (1999). J. Biol. Chem. 274, 31767-31769.
Inhibition of Biotin Carboxylase by a Reaction Intermediate Analog: Implications for the Kinetic Mechanism. Blanchard, C.Z., Amspacher, D., Strongin, R. and Waldrop, G.L. (1999). Biochem. Biophys. Res. Comm. 266, 466-471.
Overexpression and Kinetic Characterization of the Carboxyltransferase Component of Acetyl-CoA Carboxylase. Blanchard, C.Z. and Waldrop, G.L. (1998). J. Biol. Chem. 273, 19140-19145.
Three-dimensional Structure of the Biotin Carboxylase Subunit of Acetyl CoA Carboxylase. Waldrop, G.L., Rayment, I. and Holden, H.M. (1994). Biochemistry 33, 10249-10256.
Secondary 18O and Primary 13C Isotope Effects as a Probe of Transition-State Structure for Enzymatic Decarboxylation of Oxlacetate. Waldrop, G.L., Braxton, 4 of 12 B.F., Urbauer, J.L., Cleland,W.W., and Kiick, D.M. (1994). Biochemistry 33, 5262-5267.
A 70 Amino Acid Zinc-Binding Polypeptide from the Regulatory Chain of Aspartate Transcarbamoylase causes Marked Changes in the Kinetic Mechanism of the Catalytic Trimer. Zhou, B.B., Waldrop, G.L., Lum, L., and Schachman, H.K. (1994). Protein Sci. 3, 967-974.
Preliminary X-ray Crystallographic Analysis of Biotin Carboxylase Isolated from Escherichia coli. Waldrop, G., Holden, H.M., and Rayment, I. (1994). J. Mol. Biol. 235, 367-369.
15N Isotope Effects on Nonenzymatic and Aspartate Tanscarbamylase Catalyzed Reactions of Carbamyl Phospate. Waldrop, G.L., Urbauer, J.L., and Cleland, W.W. (1992). J. Am. Chem. Soc. 114, 5941-5945.
Steady-state Kinetics and Isotope Effects on the Mutant Catalytic Trimer of Aspartate Transcarbamoylase Containing the Replacement of Histidine 134 by Alanine. Waldrop, G.L., Turnbull, J.L., Parmentier, L.E., O’Leary, M.H., Cleland, W.W., and Schachman, H.K. (1992). Biochemistry 31, 6585-6591.
The Contribution of Threonine 55 to Catalysis in Aspartate Transcarbamoylase. Waldrop, G.L., Turnbull, J.L., Parmentier, L.E., Lee, S., O’Leary, M.H., Cleland, W.W., and Schachman, H.K. (1992). Biochemistry 31, 6592-6597.
Ionization of Amino Acid Residues Involved in the Catalytic Mechanism of Aspartate Transcarbamoylase. Turnbull, J.L., Waldrop, G.L., and Schachman, H.K. (1992). Biochemistry 31, 6562-6569.
Effect of Albumin on Net Copper Accumulation by Fibroblasts and Hepatocytes. Waldrop, G.L., Palida, F.A., Hadi, M., Lonergan, P.A. and Ettinger, M.J. (1990). Am. J. Physiol. 259, G219-G225.
Effect of Albumin and Histidine on the Kinetics of Copper Transport by Fibroblasts. Waldrop, G.L. and Ettinger, M.J. (1990). Am. J. Physiol. 259, G212- G218.
The Relationship of Excess Copper Accumulation by Fibroblasts from the Brindled Mouse Model of Menkes Disease to the Primary Defect. Waldrop, G.L. and Etttinger, M.J. (1990). Biochem. J. 265, 417-422.
Umbrella Sampling Simulations of Biotin Carboxylase: Is a Structure with an Open ATP Grasp Domain Stable in Solution? Novak, B.R., Moldovan, D., Waldrop, G.L. and de Queiroz, M.S. (2009). J. Phys. Chem., in press.
The Utility of Molecular Dynamics Simulations for Understanding Site-Directed Mutagenesis of Glycine Residues in Biotin Carboxylase. Bordelon, T., Nilsson Lill, S.O., and Waldrop, G.L. (2009). Proteins: Struct. Funct. Bioinf. 74, 808-819.
Structural Evidence for Substrate-Induced Synergism and Half-Sites Reactivity in Biotin Carboxylase. Mochalkin, I., Miller, J.R., Evdokimov, A., Lightle, S., Yan, C., Stover, C.K. and Waldrop, G.L. (2008). Protein Sci, 17, 1706-1718.
Molecular Dynamics Simulations of Biotin Carboxylase. Nilsson Lill, S.O., Gao, J. and Waldrop, G.L. (2008). J. Phys. Chem. B 112, 3149-3156.
DNA Inhibits Catalysis by the Carboxyltransferase Subunit of Acetyl-CoA Carboxylase: Implications for Active Site Communication. Benson, B. K., Meades, G., Jr., Grove, A., Waldrop, G.L. (2008). Prot. Sci. 17, 34-42. 2 of 12
Modeling and Numerical Simulation of Biotin Carboxylase Kinetics: Implications for Half-Sites Reactivity. de Queiroz, M.S. and Waldrop, G.L. (2007) J. Theor. Biol. 246, 167-175.
The Structure of the Carboxyltransferase Component of Acetyl-CoA Carboxylase Reveals a Zinc-binding Motif Unique to the Bacterial Enzyme. Bilder, P., Lightle, S., Bainbridge, G., Jeffrey Ohren, Barry Finzel, Fang Sun, Susan Holley, Loola Al- Kassim, Cindy Spessard, Michael Melnick, Marcia Newcomer and Waldrop,G.L. (2006) Biochemistry 279, 15772-15778.
A High Throughput Screening Assay for the Carboxyltransferase Subunit of Acetyl-CoA Carboxylase. Santoro, N., Brtva, T., Vander Roest, S., Siegel, K. and Waldrop,G.L. (2006) Analytical Biochemistry 354, 70-77.
A Novel Slow-Tight Binding Serine Protease Inhibitor from Eastern Oyster (Crassostrea virginca) plasmas Inhibits Perkinsin, the Major Extracellular Protease of the Oyster Protozoan Parasite Perkinsus marinus. Xue, Q., Waldrop, G.L., Schey, K.L., Itoh, N., Ogawa, M. Cooper, R.K., Losso, J.N., La Peyre, J. (2006) Comp. Biochem. Physiol., Part.B 145, 16-26.
The regulatory role of residues 226-232 in phosphoenolpyruvate carboxylase from maize. Yuan, J., Sayegh, J., Mendez, J., Sward, L., Sanchez, N., Sanchez, S., Waldrop, G.L. and Grover, S. (2006) Photosyn. Res. 88, 73-81.
Kinetic Characterization of Mutations found in Propionic Acidemia and Methylcrotonylglycinuria: Evidence for Cooperativity in Biotin Carboxylase. Sloane, V. and Waldrop,G.L. (2004). J. Biol. Chem. 279, 15772-15778.
Targeting Acetyl-CoA Carboxylase for Anti-Obesity Therapy. Waldrop, G.L. and Stephens, J.M. (2003). Current Med. Chem. 3, 229-234.
Multi-subunit Acetyl-CoA Carboxylases. Cronan, J.E. and Waldrop, G.L. (2002). Prog. Lipid Res. 41, 407-435.
A Biotin Analog Inhibits Acetyl-CoA Carboxylase Activity and Adipogenesis. Levert, K.L., Waldrop, G.L. and Stephens, J.M. (2002). J. Biol. Chem. 277, 16347-16350.
A Bisubstrate Analog Inhibitor of the Carboxyltransferase Component of Acetyl- CoA Carboxylase. Levert, K.L. and Waldrop, G.L. (2002). Biochem. Biophys. Res. Comm. 291, 1213-1217.
Site-Directed Mutagenesis of ATP Binding Residues of Biotin Carboxylase: Insight into the Mechanism of Catalysis. Sloane, V., Blanchard, C.Z., Guillot, F. and Waldrop, G.L. (2001). J. Biol. Chem. 276, 24991-24996. 3 of 12
Function of Escherichia coli Biotin Carboxylase Requires Catalytic Activity of Both Subunits of the Homodimer. Janiyani, K., Bordelon, T., Waldrop, G.L. and Cronan, J.E. (2001). J. Biol. Chem. 276, 29864-29870.
Benzyl, 5-(2-[2-(diethoxyphosphinoyl)acetyl]-3-oxo-7-thia-2,4- diazadicyclo[3.3.0]oct-6-yl)pentanoate, a novel biotin derivative. Amspacher, D.R., Blanchard, C.Z., Saraiva, M.C., Waldrop, G.L., Strongin, R.M. and Fronczek, F.R. (2000) Acta Crystallographica, Section C 56, E305-E306.
Do Cysteine 230 and Lysine 238 of Biotin Carboxylase Play a Role in the Activation of Biotin? Levert, K.L., Lloyd, R.B. and Waldrop, G.L. (2000). Biochemistry 39, 4122-4128.
Movement of the Biotin Carboxylase B-Domain as a Result of ATP-Binding. Thoden, J.B., Blanchard, C.Z., Holden, H.M. and Waldrop, G.L. (2000). J. Biol. Chem. 275, 16183-16190.
Mutations at Four Active Site Residues of Biotin Carboxylase Abolish Substrate- Induced Synergism by Biotin. Blanchard, C.Z., Lee, Y.M., Frantom, P.A. and Waldrop, G.L. (1999). Biochemistry, 38, 3393-3400.
Synthesis of a Reaction Intermediate Analogue of Biotin-Dependent Carboxylases via a Selective Derivatization of Biotin. Amspacher, D.R., Blanchard, C.Z., Fronczek, F.R., Saraiva, M.C., Waldrop, G.L. and Strongin, R.M. (1999). Organic Lett. 1, 99-102.
The Biotin Domain Peptide from the Biotin Carboxyl Carrier Protein of Escherichia coli Acetyl-CoA Carboxylase Causes a Marked Increase in the Catalytic Efficiency of Biotin Carboxylase and Carboxyltransferase Relative to Free Biotin. Blanchard, C.Z., Chapman-Smith, A., Wallace, J.C. and Waldrop, G.L. (1999). J. Biol. Chem. 274, 31767-31769.
Inhibition of Biotin Carboxylase by a Reaction Intermediate Analog: Implications for the Kinetic Mechanism. Blanchard, C.Z., Amspacher, D., Strongin, R. and Waldrop, G.L. (1999). Biochem. Biophys. Res. Comm. 266, 466-471.
Overexpression and Kinetic Characterization of the Carboxyltransferase Component of Acetyl-CoA Carboxylase. Blanchard, C.Z. and Waldrop, G.L. (1998). J. Biol. Chem. 273, 19140-19145.
Three-dimensional Structure of the Biotin Carboxylase Subunit of Acetyl CoA Carboxylase. Waldrop, G.L., Rayment, I. and Holden, H.M. (1994). Biochemistry 33, 10249-10256.
Secondary 18O and Primary 13C Isotope Effects as a Probe of Transition-State Structure for Enzymatic Decarboxylation of Oxlacetate. Waldrop, G.L., Braxton, 4 of 12 B.F., Urbauer, J.L., Cleland,W.W., and Kiick, D.M. (1994). Biochemistry 33, 5262-5267.
A 70 Amino Acid Zinc-Binding Polypeptide from the Regulatory Chain of Aspartate Transcarbamoylase causes Marked Changes in the Kinetic Mechanism of the Catalytic Trimer. Zhou, B.B., Waldrop, G.L., Lum, L., and Schachman, H.K. (1994). Protein Sci. 3, 967-974.
Preliminary X-ray Crystallographic Analysis of Biotin Carboxylase Isolated from Escherichia coli. Waldrop, G., Holden, H.M., and Rayment, I. (1994). J. Mol. Biol. 235, 367-369.
15N Isotope Effects on Nonenzymatic and Aspartate Tanscarbamylase Catalyzed Reactions of Carbamyl Phospate. Waldrop, G.L., Urbauer, J.L., and Cleland, W.W. (1992). J. Am. Chem. Soc. 114, 5941-5945.
Steady-state Kinetics and Isotope Effects on the Mutant Catalytic Trimer of Aspartate Transcarbamoylase Containing the Replacement of Histidine 134 by Alanine. Waldrop, G.L., Turnbull, J.L., Parmentier, L.E., O’Leary, M.H., Cleland, W.W., and Schachman, H.K. (1992). Biochemistry 31, 6585-6591.
The Contribution of Threonine 55 to Catalysis in Aspartate Transcarbamoylase. Waldrop, G.L., Turnbull, J.L., Parmentier, L.E., Lee, S., O’Leary, M.H., Cleland, W.W., and Schachman, H.K. (1992). Biochemistry 31, 6592-6597.
Ionization of Amino Acid Residues Involved in the Catalytic Mechanism of Aspartate Transcarbamoylase. Turnbull, J.L., Waldrop, G.L., and Schachman, H.K. (1992). Biochemistry 31, 6562-6569.
Effect of Albumin on Net Copper Accumulation by Fibroblasts and Hepatocytes. Waldrop, G.L., Palida, F.A., Hadi, M., Lonergan, P.A. and Ettinger, M.J. (1990). Am. J. Physiol. 259, G219-G225.
Effect of Albumin and Histidine on the Kinetics of Copper Transport by Fibroblasts. Waldrop, G.L. and Ettinger, M.J. (1990). Am. J. Physiol. 259, G212- G218.
The Relationship of Excess Copper Accumulation by Fibroblasts from the Brindled Mouse Model of Menkes Disease to the Primary Defect. Waldrop, G.L. and Etttinger, M.J. (1990). Biochem. J. 265, 417-422.
This page was last updated Thursday, September 24, 2009