Dirk Bossemeyer

Learn More
The crystal structure of the porcine heart catalytic subunit of cAMP-dependent protein kinase in a ternary complex with the MgATP analogue MnAMP-PNP and a pseudosubstrate inhibitor peptide, PKI(5-24), has been solved at 2.0 A resolution from monoclinic crystals of the catalytic subunit isoform CA. The refinement is presently at an R factor of 0.194 and the(More)
The discovery of several hundred different protein kinases involved in highly diverse cellular signaling pathways is in stark contrast to the much smaller number of known modulators of cell signaling. Of these, the H series protein kinase inhibitors (1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7), N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H8)(More)
The TrkA protein, which is essential for the activity of the constitutive Trk K+-uptake system of Escherichia coli, is a peripheral membrane protein. The protein was detected in immunoblots by polyclonal antibodies to sodium dodecyl sulfate-denatured TrkA protein. In extracts from wild-type cells equal amounts of TrkA were found in the membrane and soluble(More)
BACKGROUND Staurosporine inhibits most protein kinases at low nanomolar concentrations. As most tyrosine kinases, along with many serine/threonine kinases, are either proto oncoproteins or are involved in oncogenic signaling, the development of protein kinase inhibitors is a primary goal of cancer research. Staurosporine and many of its derivatives have(More)
The nucleotide sequence of trkA, a gene encoding a surface component of the constitutive K(+)-uptake systems TrkG and TrkH from Escherichia coli, was determined. The structure of the TrkA protein deduced from the nucleotide sequence accords with the view that TrkA is peripherally bound to the inner side of the cytoplasmic membrane. Analysis by a dot matrix(More)
Escherichia coli cells which contain a functional Kup (formerly TrkD) system took up Cs+ with a moderate rate and affinity. Kup is a separate K+ uptake system with relatively little discrimination in the transport of the cations K+, Rb+, and Cs+. Regardless of the presence or absence of Kup, K+-replete cells took up Cs+ primarily by a very low affinity(More)
Evolution favours the use of glycine-rich loops for nucleotide binding in proteins. In the large family of protein kinases, the catalytic domain of which has one of the highest degrees of conservation among all known proteins, the structure of the nucleotide-binding site differs from classical folds. We are now beginning to understand the multiple(More)
A structural feature shared by many protein kinases is the requirement for phosphorylation of threonine or tyrosine in the so-called activation loop for full enzyme activity. Previous studies by several groups have indicated that the isotypes alpha, betaI, and betaII of protein kinase C (PKC) are synthesized as inactive precursors and require(More)
The solution of crystal structures from half a dozen protein kinases during the last four years in different laboratories has deepened our understanding of the catalysis and regulation of this enzyme class, and given a vigorous impetus to the whole field. Due to the great degree of sequence conservation among protein kinases the informational yield with(More)
The catalytic subunit of recombinant wild-type cyclic adenosine monophosphate-dependent protein kinase A (PKA) has been analyzed by a combination of 1D gel electrophoresis, in-gel digestion by trypsin, chymotrypsin, or endoproteinase AspN, and nano-ultraperformance liquid chromatography--MS/MS. The MS/MS spectra were annotated by MASCOT and the annotations(More)