Dataset Information

PeSTK db a comprehensive data repository of Probiotic Serine Threonine kinases.

ABSTRACT: The signal transduction pathway of prokaryotes involves a peptidoglycan synthesis cluster (PG) to sense external stimuli. One of the major components of the PG synthesis cluster is protein kinases (pknA - G). The sequence data of probiotic eSTKs (Eukaryotic like Serine, Threonine kinases) are obscure, scarce and essentially required to understand the role of probiotic microbes in combating infectious diseases. The most essential need to understand and develop certain therapeutic drugs against pathogens is the eSTK sequence data. Hence, we developed a comprehensive user-friendly data repository of probiotic eSTK's (PeSTK), which holds 830 STK sequences. Therefore, the data resource of PeSTK developed is unique, an open-access very summative containing various probiotic eSTK's in a single locality. The sequence datasets of the eSTK developed with easy-to-operate browsing as well as searching. Therefore, eSTK data resources should be useful for sequence-based studies and drug development. The sequence datasets are available at Figshare Digital Object Identifier/DOI of the sequences is https://doi.org/10.6084/m9.figshare.146606 .

SUBMITTER: Lokesh D

PROVIDER: S-EPMC9178022 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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PeSTK db a comprehensive data repository of Probiotic Serine Threonine kinases.

Lokesh Dhanashree D Psn Suresh S Kammara Rajagopal R

Scientific data 20220608 1

The signal transduction pathway of prokaryotes involves a peptidoglycan synthesis cluster (PG) to sense external stimuli. One of the major components of the PG synthesis cluster is protein kinases (pknA - G). The sequence data of probiotic eSTKs (Eukaryotic like Serine, Threonine kinases) are obscure, scarce and essentially required to understand the role of probiotic microbes in combating infectious diseases. The most essential need to understand and develop certain therapeutic drugs against pa ...[more]

PMID: 35676297

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Project description:BACKGROUND: Serine/threonine kinases (STKs) have been found in an increasing number of prokaryotes, showing important roles in signal transduction that supplement the well known role of two-component system. Cyanobacteria are photoautotrophic prokaryotes able to grow in a wide range of ecological environments, and their signal transduction systems are important in adaptation to the environment. Sequence information from several cyanobacterial genomes offers a unique opportunity to conduct a comprehensive comparative analysis of this kinase family. In this study, we extracted information regarding Ser/Thr kinases from 21 species of sequenced cyanobacteria and investigated their diversity, conservation, domain structure, and evolution. RESULTS: 286 putative STK homologues were identified. STKs are absent in four Prochlorococcus strains and one marine Synechococcus strain and abundant in filamentous nitrogen-fixing cyanobacteria. Motifs and invariant amino acids typical in eukaryotic STKs were conserved well in these proteins, and six more cyanobacteria- or bacteria-specific conserved residues were found. These STK proteins were classified into three major families according to their domain structures. Fourteen types and a total of 131 additional domains were identified, some of which are reported to participate in the recognition of signals or substrates. Cyanobacterial STKs show rather complicated phylogenetic relationships that correspond poorly with phylogenies based on 16S rRNA and those based on additional domains. CONCLUSION: The number of STK genes in different cyanobacteria is the result of the genome size, ecophysiology, and physiological properties of the organism. Similar conserved motifs and amino acids indicate that cyanobacterial STKs make use of a similar catalytic mechanism as eukaryotic STKs. Gene gain-and-loss is significant during STK evolution, along with domain shuffling and insertion. This study has established an overall framework of sequence-structure-function interactions for the STK gene family, which may facilitate further studies of the role of STKs in various organisms.

Project description:Inactive conformations of protein kinase catalytic domains where the DFG motif has a "DFG-out" orientation and the activation loop is folded present a druggable binding pocket that is targeted by FDA-approved 'type-II inhibitors' in the treatment of cancers. Tyrosine kinases (TKs) typically show strong binding affinity with a wide spectrum of type-II inhibitors while serine/threonine kinases (STKs) usually bind more weakly which we suggest here is due to differences in the folded to extended conformational equilibrium of the activation loop between TKs vs. STKs. To investigate this, we use sequence covariation analysis with a Potts Hamiltonian statistical energy model to guide absolute binding free-energy molecular dynamics simulations of 74 protein-ligand complexes. Using the calculated binding free energies together with experimental values, we estimated free-energy costs for the large-scale (~17-20 Å) conformational change of the activation loop by an indirect approach, circumventing the very challenging problem of simulating the conformational change directly. We also used the Potts statistical potential to thread large sequence ensembles over active and inactive kinase states. The structure-based and sequence-based analyses are consistent; together they suggest TKs evolved to have free-energy penalties for the classical 'folded activation loop' DFG-out conformation relative to the active conformation, that is, on average, 4-6 kcal/mol smaller than the corresponding values for STKs. Potts statistical energy analysis suggests a molecular basis for this observation, wherein the activation loops of TKs are more weakly 'anchored' against the catalytic loop motif in the active conformation and form more stable substrate-mimicking interactions in the inactive conformation. These results provide insights into the molecular basis for the divergent functional properties of TKs and STKs, and have pharmacological implications for the target selectivity of type-II inhibitors.

Dataset Information

PeSTK db a comprehensive data repository of Probiotic Serine Threonine kinases.

Publications

PeSTK db a comprehensive data repository of Probiotic Serine Threonine kinases.

Similar Datasets

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