Structure prediction and functional characterization of uncharacterized protein Rv1708 of Mycobacterium tuberculosis (Strain ATCC 25618/H37Rv)

ABSTRACT The mycobacterial phosphoglycosyltransferase WecA, which initiates arabinogalactan biosynthesis in Mycobacterium tuberculosis, has been proposed as a target of the caprazamycin derivative CPZEN-45, a preclinical drug candidate for the treatment of tuberculosis. In this report, we describe the functional characterization of mycobacterial WecA and confirm the essentiality of its encoding gene in M. tuberculosis by demonstrating that the transcriptional silencing of wecA is bactericidal in vitro and in macrophages. Silencing wecA also conferred hypersensitivity of M. tuberculosis to the drug tunicamycin, confirming its target selectivity for WecA in whole cells. Simple radiometric assays performed with mycobacterial membranes and commercially available substrates allowed chemical validation of other putative WecA inhibitors and resolved their selectivity toward WecA versus another attractive cell wall target, translocase I, which catalyzes the first membrane step in the biosynthesis of peptidoglycan. These assays and the mutant strain described herein will be useful for identifying potential antitubercular leads by screening chemical libraries for novel WecA inhibitors.

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Lipopolysaccharide isolated from Mycobacterium tuberculosis strain Aoyama B.

Agricultural and Biological Chemistry ◽

10.1271/bbb1961.51.691 ◽

1987 ◽

Vol 51 (3) ◽

pp. 691-697 ◽

Cited By ~ 1

Author(s):

Hiroshi KOBATAKE ◽

Kazuhiro KUMAGAI ◽

Osamu KITAGAWA ◽

Sei-ichi NIWA

Keyword(s):

Mycobacterium Tuberculosis ◽

Tuberculosis Strain ◽

Mycobacterium Tuberculosis Strain

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Comparison of the proteome of Mycobacterium tuberculosis strain H37Rv with clinical isolate CDC 1551

Microbiology ◽

10.1099/00221287-146-12-3205 ◽

2000 ◽

Vol 146 (12) ◽

pp. 3205-3216 ◽

Cited By ~ 69

Author(s):

Joanna C. Betts ◽

Paul Dodson ◽

Selwyn Quan ◽

Alan P. Lewis ◽

Pam J. Thomas ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Clinical Isolate ◽

Tuberculosis Strain ◽

Strain H37rv ◽

Mycobacterium Tuberculosis Strain

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Homology modeling and functional characterization of multidrug effluxor Mta protein from Bacillus Atrophaeus: An explanatory insilico approach

10.1101/2020.12.29.424731 ◽

2020 ◽

Author(s):

Mohammad Rejaur Rahman ◽

Ishtiak Malique Chowdhury ◽

Anik Banik ◽

Emran Hossain Sajib

Keyword(s):

Function Analysis ◽

Functional Characterization ◽

Bacillus Atrophaeus ◽

Uncharacterized Protein ◽

Protein Protein Interaction ◽

Functional Aspects ◽

Resistance Function ◽

Spore Forming Bacteria ◽

Protein Pocket

AbstractPhenotypically similar to B. subtilis, Bacillus atrophaeus is a Gram-positive, aerobic, spore-forming bacteria. It is a black-pigmented bacterial genus. Therefore, it is of interest to study the uncharacterized proteins in the genome. For a detailed computational sequence-structure-function analysis using available data and resources, an uncharacterized protein Mta (AKL87074.1) in the genome was selected. In this study, attempts were made to study the physicochemical properties, predict secondary structure, modeling the 3-D protein, pocket identification, protein-protein interaction and phylogenetic analysis of Mta protein. The predicted active site using CASTp is analyzed for understanding their multidrug resistance function. Because Mta is a MerR family member, these investigations on these functional aspects could lead us for better understanding of antibiotic resistance phenomenon.

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