Increasing the kinase specificity of k252a by protein surface recognition.
[reaction: see text] Here we describe a miniature protein (1) that presents the cAMP-dependent protein kinase (PKA) recognition epitope found within the heat-stable Protein Kinase Inhibitor protein (PKI) and a miniature protein conjugate (1-K252a) in which 1 is joined covalently to the high-affinity but nonselective kinase inhibitor K252a. Miniature protein 1 recognizes PKA with an affinity that rivals that of PKI and, in the context of 1-K252a, leads to a dramatic increase in kinase specificity.
Schneider
Tanya L
TL
Department of Chemistry and Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520-8107, USA.
Mathew
Rebecca S
RS
Rice
Kevin P
KP
Tamaki
Kazuhiko
K
Wood
John L
JL
Schepartz
Alanna
A
D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D026121:Indole Alkaloids; D047908:Intracellular Signaling Peptides and Proteins; D015394:Molecular Structure; D013379:Substrate Specificity
D002227:Carbazoles; D026121:Indole Alkaloids; D047908:Intracellular Signaling Peptides and Proteins; C015482:protein kinase modulator; C049985:staurosporine aglycone; D017868:Cyclic AMP-Dependent Protein Kinases