Structural analysis of Staphylococcus aureus serine/threonine kinase PknB.
Effective treatment of infections caused by the bacterium Staphylococcus aureus remains a worldwide challenge, in part due to the constant emergence of new strains that are resistant to antibiotics. The serine/threonine kinase PknB is of particular relevance to the life cycle of S. aureus as it is involved in the regulation of purine biosynthesis, autolysis, and other central metabolic processes of the bacterium. We have determined the crystal structure of the kinase domain of PknB in complex with a non-hydrolyzable analog of the substrate ATP at 3.0 Å resolution. Although the purified PknB kinase is active in solution, it crystallized in an inactive, autoinhibited state. Comparison with other bacterial kinases provides insights into the determinants of catalysis, interactions of PknB with ligands, and the pathway of activation.
Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Sonja
S
Rakette
Stefanie
S
Donat
Knut
K
Ohlsen
Thilo
T
Stehle
D003001:Cloning, Molecular; D003460:Crystallization; D004591:Electrophoresis, Polyacrylamide Gel; D013058:Mass Spectrometry; D008958:Models, Molecular; D010766:Phosphorylation; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D013211:Staphylococcus aureus / Q000201:enzymology*; D014961:X-Ray Diffraction
D017346:Protein Serine-Threonine Kinases