title: Identification and structural-functional analysis of cyclin-dependent kinases of the cattle tick Rhipicephalus (Boophilus) microplus.
abstract: Cyclin-dependent kinases (CDKs) are a family of serine/threonine kinases essential for cell cycle progression. Herein, we describe the participation of CDKs in the physiology of Rhipicephalus microplus, the southern cattle tick and an important disease vector. Firstly, amino acid sequences homologous with CDKs of other organisms were identified from a R. microplus transcriptome database in silico. The analysis of the deduced amino acid sequences of CDK1 and CDK10 from R. microplus showed that both have caspase-3/7 cleavage motifs despite their differences in motif position and length of encoded proteins. CDK1 has two motifs (DKRGD and SAKDA) located opposite to the ATP binding site while CDK10 has only one motif (SLLDN) for caspase 3-7 near the ATP binding site. Roscovitine (Rosco), a purine derivative that inhibits CDK/cyclin complexes by binding to the catalytic domain of the CDK molecule at the ATP binding site, which prevents the transfer of ATP's γphosphoryl group to the substrate. To determine the effect of Rosco on tick CDKs, BME26 cells derived from R. microplus embryo cells were utilized in vitro inhibition assays. Cell viability decreased in the Rosco-treated groups after 24 hours of incubation in a concentration-dependent manner and this was observed up to 48 hours following incubation. To our knowledge, this is the first report on characterization of a cell cycle protein in arachnids, and the sensitivity of BME26 tick cell line to Rosco treatment suggests that CDKs are potential targets for novel drug design to control tick infestation.
authors.affiliation: Laboratório Integrado de Bioquímica Hatisaburo Masuda, NUPEM - UFRJ, campus Macaé, Avenida São José do Barreto, São José do Barreto, Macaé, RJ, Brazil ; Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, CCS, Bloco H, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
authors.forename: Helga
authors.initials: H
authors.lastname: Gomes
authors.forename: Nelilma C
authors.initials: NC
authors.lastname: Romeiro
authors.forename: Gloria R C
authors.initials: GR
authors.lastname: Braz
authors.forename: Eduardo Alves Gamosa
authors.initials: EA
authors.lastname: de Oliveira
authors.forename: Camilla
authors.initials: C
authors.lastname: Rodrigues
authors.forename: Rodrigo Nunes
authors.initials: RN
authors.lastname: da Fonseca
authors.forename: Naftaly
authors.initials: N
authors.lastname: Githaka
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Isezaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Konnai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ohashi
authors.forename: Itabajara
authors.initials: I
authors.lastname: da Silva Vaz
authors.forename: Carlos
authors.initials: C
authors.lastname: Logullo
authors.forename: Jorge
authors.initials: J
authors.lastname: Moraes
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D060829:Arthropod Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D020169:Caspases / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011687:Purines / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D048494:Rhipicephalus / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000077546:Roscovitine; D012469:Salivary Glands / Q000166:cytology / Q000187:drug effects; D016415:Sequence Alignment; D040681:Structural Homology, Protein
chemical_list: D060829:Arthropod Proteins; D047428:Protein Kinase Inhibitors; D011687:Purines; D011994:Recombinant Proteins; D000077546:Roscovitine; D000255:Adenosine Triphosphate; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases; D020169:Caspases