In Silico Study of Coumarin Derivatives Against Enoyl ACP Reductase, Ornithine Acetyltransferase and Protein Kinase B Target Enzymes of Mycobacterium tuberculosis

Curcuma xanthorrhiza Roxb and Tamarindus indica L. have been used for a long time by Indonesia local societies as tuberculosis therapy. This study explores the active compounds of Curcuma xanthorrhiza Roxb and Tamarindus indica L that important for suppressing the survival of Mycobacterium tuberculosis and predicts the pharmacokinetics and toxicity of the compounds. stringApp of Cytoscape 3.6.0 was used for screening the compounds targeting mycobacteria proteins, then computational tools like SwissADME (http://swissadme.ch/) and admetSAR (http://lmmd.ecust.edu.cn/admetsar1/predict/) were applied for estimating absorption, distribution, metabolism, excretion, and toxicity (ADMET) of active compounds. The result has been shown that there were some active compounds could target proteins of Mycobacterium tuberculosis. According to the profiling result, these compounds had a various characteristic in gastrointestinal absorption, could pass the blood-brain barrier, and had drug-like properties. In toxicity term, the active compounds did not cause Ames toxicity.

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In silico Study, Protein Kinase Inhibition and Antiproliferative Potential of Flavonoids Isolated from Bassia eriophora (Schrad.) Growing in KSA

Indian Journal of Pharmaceutical Education and Research ◽

10.5530/ijper.55.2.86 ◽

2021 ◽

Vol 55 (2) ◽

pp. 483-490

Author(s):

Arafa Musa ◽

Mohammad Mahmoud Al-Sanea ◽

Nasser Hadal Alotaibi ◽

Taghreed Stum Alnusaire ◽

Shaimaa Rashad Ahmed ◽

...

Keyword(s):

Protein Kinase ◽

In Silico ◽

Kinase Inhibition ◽

Protein Kinase Inhibition ◽

In Silico Study

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Protein kinase B controls Mycobacterium tuberculosis growth via phosphorylation of the global transcriptional regulator Lsr2

10.1101/571406 ◽

2019 ◽

Author(s):

Kawther Alqaseer ◽

Obolbek Turapov ◽

Philippe Barthe ◽

Heena Jagatia ◽

Angélique De Visch ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Protein Kinase ◽

Dna Binding ◽

Protein Kinase B ◽

Transcriptional Regulator ◽

The Body ◽

Altered Expression ◽

Chip Sequencing ◽

Essential Protein ◽

Wide Range

ABSTRACTMycobacterium tuberculosis is able to persist in the body through months of multi-drug therapy. Mycobacteria possess a wide range of regulatory proteins, including the essential protein kinase B (PknB), that control transitions between growth states. Here, we establish that depletion of PknB in replicating M. tuberculosis results in transcriptional adaptations that implicate the DNA-binding protein Lsr2 in coordinating these changes. We show that Lsr2 is phosphorylated by PknB, and that phosphorylation of Lsr2 at threonine 112 is important for M. tuberculosis growth and survival under hypoxic conditions. Fluorescence anisotropy and electrophoretic mobility shift assays demonstrate that phosphorylation reduces Lsr2 binding to DNA, and ChIP-sequencing confirms increased DNA binding of a phosphoablative (T112A) Lsr2 mutant in M. tuberculosis. Altered expression of target genes in T112A Lsr2 compared to wild type Lsr2 M. tuberculosis offers further evidence that phosphorylation mediates expression of the Lsr2 regulon. Structural studies reveal increased dynamics of the Lsr2 DNA binding domain from a T112D phosphomimetic Lsr2 mutant, providing a molecular basis for decreased DNA binding by phosphorylated Lsr2. Our findings suggest that, the essential protein kinase, PknB controls M. tuberculosis growth and adaptations to the changing host environment by phosphorylating the global transcriptional regulator Lsr2.

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