title: Bacterial eukaryotic type serine-threonine protein kinases: from structural biology to targeted anti-infective drug design.
abstract: Signaling through protein kinases is an evolutionary conserved, widespread language of biological regulation. The eukaryotic type serine-threonine protein kinases (STPKs) found in normal human microbiote and in pathogenic bacteria play a key role in regulation of microbial survival, virulence and pathogenicity. Therefore, down-regulation of bacterial STPKs emerges as an attractive approach to cure infections. In this review we focused on actinobacterial STPKs to demonstrate that these enzymes can be used for crystal structure studies, modeling of 3D structure, construction of test systems and design of novel chemical libraries of low molecule as weight inhibitors. In particular, the prototypic pharmacological antagonists of Mycobacterium tuberculosis STPKs are perspective for development of a novel generation of drugs to combat the socially important disease. These inhibitors may modulate both actinobacterial and host STPKs and trigger programmed death of pathogenic bacteria.
authors.affiliation: Vavilov Institute of General Genetics, Russian Federation. valerid@rutenia.ru
authors.forename: Valery N
authors.initials: VN
authors.lastname: Danilenko
authors.forename: Dmitry I
authors.initials: DI
authors.lastname: Osolodkin
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Lakatosh
authors.forename: Maria N
authors.initials: MN
authors.lastname: Preobrazhenskaya
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Shtil
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D015195:Drug Design; D005057:Eukaryotic Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases