Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases.
A family of eukaryotic-like Ser/Thr protein kinases occurs in bacteria, but little is known about the structures and functions of these proteins. Here we characterize PknB, a transmembrane signaling kinase from Mycobacterium tuberculosis. The intracellular PknB kinase domain is active autonomously, and the active enzyme is phosphorylated on residues homologous to regulatory phospho-acceptors in eukaryotic Ser/Thr kinases. The crystal structure of the PknB kinase domain in complex with an ATP analog reveals the active conformation. The predicted fold of the PknB extracellular domain matches the proposed targeting domain of penicillin-binding protein 2x. The structural and chemical similarities of PknB to metazoan homologs support a universal activation mechanism of Ser/Thr protein kinases in prokaryotes and eukaryotes.
Young
Tracy A
TA
Department of Molecular and Cell Biology, 229 Stanley Hall 3206, University of California, Berkeley, California 94720-3206, USA.
Delagoutte
Benedicte
B
Endrizzi
James A
JA
Falick
Arnold M
AM
Alber
Tom
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004789:Enzyme Activation / Q000502:physiology; D005057:Eukaryotic Cells / Q000201:enzymology; D005109:Extracellular Matrix / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D046915:Penicillin-Binding Proteins; D010766:Phosphorylation; D011487:Protein Conformation; D011493:Protein Kinase C / Q000737:chemistry* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D040681:Structural Homology, Protein
D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; C072223:PBP 2x protein, Streptococcus; D000255:Adenosine Triphosphate; C061570:protein kinase N; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C