326 Goss Laboratory
1925 Coffey Rd
Columbus, OH 43210
The focus of Dr. Brooks' research is to identify and understand the function of structural motifs that participate in initiating changes in protein conformation and function. The mechanisms by which molecules rearrange their constituent atoms and modulate their functions are not well understood. Does each protein have a unique mechanisms to alter its shape, or are there a discrete number of recognizable motifs/mechanisms that are used in various proteins to alter shape and thereby modulate function? Both post-translational modifications or protein/protein interactions can initiate conformation changes that regulate function. Numerous post-translational modifications affect protein shape and function, including: metal prosthetic groups (such as zinc- binding in lactogenic hormones or calcium-binding in calmodulin or alpha-lactalbumin), or phosphorylation (such as phosphorylation of casein, prolactin, growth hormone or calmodulin). The binding of hormones and receptors are protein/protein interacts that may induce conformation changes that modulate function. The amino acids in proteins that are directly affected by these interactions and pot translational modifications have not been identified in most proteins and common motifs that contain such residues have not been classified.
The mechanism by which local conformation changes are initiated and transmitted to distal structural elements need to be identified. This information is required in order to engineer enzymes for industrial applications that may be regulated, design peptides and proteins with pharmaceutical applications, understand the basis of diseases that are associated with mutations and loss of functional regulation, and to understand the relationship of conserved protein structures during the evolution of species.
Currently, three groups of proteins are being investigated: somatotropic and lactogenic hormones (functional motifs: protein/receptor binding, zinc-binding and phosphorylation), alpha-lactalbumin (calcium-binding and zinc-binding) and calmodulin (phosphorylation and calcium binding).
Pemlykov, S.E., Veprintsev, D.B., Brooks, C.L., Permykov, E.A. and Berliner, L.J. Bovine alpha-lactalbumin: Searching for the Strong Zinc-binding Site. Proteins: Structure, Function and Genetics 40: 106-111 (2000).
Peterson, F.C. and Brooks, C.L. The Species Specificity of Growth Hormone Requires the Cooperative Interaction of Two Motifs. FEBS Letters 3.1276-282 (2000).
Veprintsev, D.B., Naryan, M, Perrnyakov, S.E., Uversky, V.N., Brooks, C.L., Cherskaya, A.M., Perrnyakov, E.A. and Berliner, L.J. Fine Tuning the N-terrninus of a Calcium Binding Protein alpha-lactalbumin. Proteins: Structure, Function and Genetics 31: 65-72 (1999).
Wicks, J .R. and Brooks, C.L. Growth Hormone Kinase Activity in Bovine Anterior Pituitary Subcellular Fractions. Endocrine 10: 77-82 (1999).
Duda, K.M. and Brooks, C.L. Human Growth Hormone Site 2 Lactogenic Activity Requires a Distant Tyrosine 164. FEBS Letters, 442: 120-124 (1999).
Peterson, F.C. Anderson, P.l., Berliner, L.l. and Brooks, C.L. Efficient Expression, Folding and Characterization of Small Molecular Weight Proteins with a pT7-7 -derived Phagemid. Protein Expression and Purification, 15: 16-23 (1999).
Wicks, J .R. and Brooks, C.L. Prolactin Kinase Activity in Bovine Anterior Pituitary Subcellular Fractions. Molec. Cell. Endo. 141: 125-132 (1999).
Brooks, C.L. and Saiduddin, S. Phosphorylation of Bovine Prolactin Eliminates Luteotrophic Activity in the Rat. Life Sciences 63: 1281-1287 (1998).
Anderson, P .J. , Brooks, C.L and L.1. Berliner. Functional Identification of Calcium Binding Residues in Bovine alpha-Lactalbumin. Biochemistry 16: 11648-11643 (1997).
Peterson, F.C. and Brooks, C.L. Identification of a Lactogenic Motif in Human Growth Hormone. Journal of Biological Chemistry 212: 21444-21448 (1997).
Permyakov, E.A., D.B. Veprintsev, G.Y. Deikus, S.E. Permyakov, L.P. Kalinichenko, V.M. Grishchenko and Brooks, C.L. pH-Induced Transition and Zn2+-binding Properties of Bovine Prolactin. FEBS Letters 405: 273-276 (1997).
Frazer, G.S., D.M. Bucci and Brooks, C.L. Two-Dimensional Polyacrylamide Gel Electrophoresis of Bovine Semen After Cryopreservation in Half Milliliter Straws. Theriogenology 46: 1103-1115 (1996).
Schenck, P.A., D.J. Chew, and Brooks, C.L. Effects of Storage on Serum Ionized Calcium and pH from Horses with Normal and Abnormal Ionized Calcium. Veterinary Clinical Pathology 25: 118-120 (1996).
Oglesbee, M. , Z. Liu, H. Kenney and Brooks, C.L. The Highly Inducible Member of the 70kDa Family of Heat Shock Proteins Increases Canine Distemper Virus Polymerase Activity. Journal General Virology 77: 2125-2135 (1996).
Schenck, P.A., D.J. Chew, and Brooks, C.L. Fractionation of Canine Serum Calcium Using a Micropartition System. American Journal of Veterinary Research 57: 268-271 (1996).
Maceijewski, P .M. , F .C. Peterson, P .J . Anderson, and Brooks, C.L. Mutation of Serine 90 to Glutamic Acid Mimics Phosphorylation of Bovine Prolactin. Journal of Biological Chemistry 210: 27661-27665 (1995).
Wicks, J .R. and Brooks, C.L. Biological Activity of Phosphorylated and Dephosphorylated Bovine Prolactin. Molecular and Cellular Endocrinology 112: 223-229 (1995).
Latendresse, J.R., Brooks, C.L, and C.C. Capen. Toxic Effects of Butylated Triphenyl Phosphate-based Hydraulic Fluid and Tricrencyl Phosphate in Female F344 rats. Veterinary Pathology 32: 394-402 (1995).
Schenck, P.A., D.J. Chew, and Brooks, C.L. Effects of Storage on Serum Ionized Calcium and pH values in Clinically Normal Dogs. American Journal of Veterinary Research 56 (3), 304-307 (1995).