Multimedia in Biochemistry and Molecular Biology Education Proteopedia Entry: “Eukaryotic Protein Kinase Catalytic Domain”
Alice C. Harmon*
From the Department of Biology, UF Genetics Institute, and Program in Plant Molecular and Cellular Biology, University of Florida, Gainesville, Florida 32611-8525
Protein kinases play central roles in regulating eukaryotic developmental and physiological processes. This tutorial uses the catalytic subunit of cyclic-nucleotide-dependent protein kinase (protein kinase A or PKA) as a model to illustrate the structural and functional elements conserved in the catalytic domains of these important enzymes. The first part of the tutorial shows in three-dimensional structure the locations of the 12 subdomains that are conserved in the primary structure. This walk-through of the subdomains shows how each contributes to the core structure of the protein kinase fold or to ATP-binding and catalysis. The second part illustrates internal structures formed from residues that are not contiguous in the primary structure and shows the features of the activation loop. The last part
FIG 1
compares three conformations of PKA side-by-side. The first is an inactive conformation in which the activation loop is not phosphorylated, and the others are open and closed conformations of active enzymes that represent structural changes that may occur during the catalytic cycle. Each of these structures is examined at three levels—the relationship of the small and large lobes, the internal core structures, and the locations of residues critical for activity (Fig. 1). This interactive tutorial (available at http://www.proteopedia.org/wiki/index.php/Eukaryotic_Protein_Kinase_Catalytic_Domain) will help students learn how the primary and tertiary structures of protein kinases are related and which structural elements are critical for activity.
Comparison of inactive and active conformations of the catalytic domain of protein kinase A. Residues critical for activity are shown in ball and stick. Structures shown in color are: Mg21-binding/activation loop, gold; catalytic loop, blue; C-helix, orchid. The active structure (right) with bound Mg21 (green space fill) and ATP (stick) shows a fully formed, closed active site, and the center structure has an empty active site in open conformation. The inactive structure (left) shows the active site is malformed with critical residues out of alignment.
*Address for correspondence to: Department of Biology, UF Genetics Institute, and Program in Plant Molecular and Cellular Biology, University of Florida, Gainesville, FL 32611-8525. E-mail: [email protected]. Received 16 December 2013; Accepted 16 January 2014 DOI 10.1002/bmb.20782 Published online 18 February 2014 in Wiley Online Library (wileyonlinelibrary.com)
Biochemistry and Molecular Biology Education
275
Alice C. Harmon*
From the Department of Biology, UF Genetics Institute, and Program in Plant Molecular and Cellular Biology, University of Florida, Gainesville, Florida 32611-8525
Protein kinases play central roles in regulating eukaryotic developmental and physiological processes. This tutorial uses the catalytic subunit of cyclic-nucleotide-dependent protein kinase (protein kinase A or PKA) as a model to illustrate the structural and functional elements conserved in the catalytic domains of these important enzymes. The first part of the tutorial shows in three-dimensional structure the locations of the 12 subdomains that are conserved in the primary structure. This walk-through of the subdomains shows how each contributes to the core structure of the protein kinase fold or to ATP-binding and catalysis. The second part illustrates internal structures formed from residues that are not contiguous in the primary structure and shows the features of the activation loop. The last part
FIG 1
compares three conformations of PKA side-by-side. The first is an inactive conformation in which the activation loop is not phosphorylated, and the others are open and closed conformations of active enzymes that represent structural changes that may occur during the catalytic cycle. Each of these structures is examined at three levels—the relationship of the small and large lobes, the internal core structures, and the locations of residues critical for activity (Fig. 1). This interactive tutorial (available at http://www.proteopedia.org/wiki/index.php/Eukaryotic_Protein_Kinase_Catalytic_Domain) will help students learn how the primary and tertiary structures of protein kinases are related and which structural elements are critical for activity.
Comparison of inactive and active conformations of the catalytic domain of protein kinase A. Residues critical for activity are shown in ball and stick. Structures shown in color are: Mg21-binding/activation loop, gold; catalytic loop, blue; C-helix, orchid. The active structure (right) with bound Mg21 (green space fill) and ATP (stick) shows a fully formed, closed active site, and the center structure has an empty active site in open conformation. The inactive structure (left) shows the active site is malformed with critical residues out of alignment.
*Address for correspondence to: Department of Biology, UF Genetics Institute, and Program in Plant Molecular and Cellular Biology, University of Florida, Gainesville, FL 32611-8525. E-mail: [email protected]. Received 16 December 2013; Accepted 16 January 2014 DOI 10.1002/bmb.20782 Published online 18 February 2014 in Wiley Online Library (wileyonlinelibrary.com)
Biochemistry and Molecular Biology Education
275
