Identification and classification of small molecule kinases: insights into substrate recognition and specificityReport as inadecuate

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BMC Evolutionary Biology

, 16:7

Genome evolution and evolutionary systems biology


BackgroundMany prokaryotic kinases that phosphorylate small molecule substrates, such as antibiotics, lipids and sugars, are evolutionarily related to Eukaryotic Protein Kinases EPKs. These Eukaryotic-Like Kinases ELKs share the same overall structural fold as EPKs, but differ in their modes of regulation, substrate recognition and specificity—the sequence and structural determinants of which are poorly understood.

ResultsTo better understand the basis for ELK specificity, we applied a Bayesian classification procedure designed to identify sequence determinants responsible for functional divergence. This reveals that a large and diverse family of aminoglycoside kinases, characterized members of which are involved in antibiotic resistance, fall into major sub-groups based on differences in putative substrate recognition motifs. Aminoglycoside kinase substrate specificity follows simple rules of alternating hydroxyl and amino groups that is strongly correlated with variations at the DFG + 1 position.

ConclusionsSubstrate specificity determining features in small molecule kinases are mostly confined to the catalytic core and can be identified based on quantitative sequence and crystal structure comparisons.

KeywordsKinase superfamily Aminoglycoside kinase Antibiotic resistance Substrate specificity Enzyme evolution AbbreviationsEPKeukaryotic protein kinases

ELKEPK-like kinases

APKatypical protein kinases

mcBPPSmultiple category bayesian partitioning with pattern selection

APHaminoglycoside phosphotransferases

Electronic supplementary materialThe online version of this article doi:10.1186-s12862-015-0576-x contains supplementary material, which is available to authorized users.

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Author: Krishnadev Oruganty - Eric E. Talevich - Andrew F. Neuwald - Natarajan Kannan


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