Mycobacterium leprae ML0314c LipU Secreted carboxyl esterase
Comment
ML0314c showed preference for short carbon chain substrates with maximum activity for pNP-acetate. Secreted carboxyl esterase that could modulate the immune response in leprosy patients. Inhibited by Eserine, DEPC and Orlistat
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.) > cellular organisms: NE > Bacteria: NE > Terrabacteria group: NE > Actinobacteria [phylum]: NE > Actinobacteria [class]: NE > Corynebacteriales: NE > Mycobacteriaceae: NE > Mycobacterium: NE > Mycobacterium leprae: NE
Warning: This entry is a compilation of different species or line or strain with more than 90% amino acid identity. You can retrieve all strain data
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.) Mycobacterium leprae Br4923: N, E.
Mycobacterium leprae TN: N, E.
Mycobacterium leprae 3125609: N, E.
LegendThis sequence has been compared to family alignement (MSA) red => minority aminoacid blue => majority aminoacid color intensity => conservation rate title => sequence position(MSA position)aminoacid rate Catalytic site Catalytic site in the MSA MAISAGAPVEIVESGPSIAARLASLTSRLTIRPILAVGSYVPQLPWPFGL IDHAARVLLPVTNAARAEVNLSNTSAQLVRAAGVRPADGSGRIVLYLHGG AFLGCGANSHRRLVETLSKLADSPILVVNYRLLPKHSIGMALDDCHDGYQ WLRRLGYDPEQIVLAGDSAGGYLALALAQRLQDVGEEPAALVAISPLLQL AKKGKQAHPNAKTDAMFPPKAFDALGRLVASSAAKNKVDDKPEELYEPLD HIAPGLPRTLIHVSGSEVLLHDAQLAATKLAAVGVPAEIRVWPGQVHVFQ AAAPMVPEATLSLRQISQYIREATASKASRDRQSL
References
Title: Characterization of ML0314c of Mycobacterium leprae and deciphering its role in the immune response in leprosy patients Kaur G, Sharma A, Narang T, Dogra S, Kaur J Ref: Gene, 643:26, 2018 : PubMed
Mycobacterium leprae has a reduced genome size due to the reductive evolution over a long period of time. Lipid metabolism plays an important role in the life cycle and pathogenesis of this bacterium. In comparison to 26 lip genes (Lip A-Z) of M. tuberculosis, M. leprae retained only three orthologs indicating their importance in its life cycle. ML0314c (LipU) is one of them. It is conserved throughout the mycobacterium species. Bioinformatics analysis showed the presence of an alpha/beta hydrolase fold and 'GXSXG' characteristic of the esterases/lipases. The gene was expressed in E. coli and purified to homogeneity. It showed preference towards short chain esters with pNP-acetate as the preferred substrate. The enzyme showed optimal activity at 45 degrees C and pH8.0. ML0314c protein was stable between temperatures ranging from 20 to 60 degrees C and pH5.0-8.0, i.e., relatively acidic and neutral conditions. The active site residues predicted bioinformatically were confirmed to be Ser168, Glu267, and His297 by site directed mutagenesis. E-serine, DEPC and Tetrahydrolipstatin (THL) completely inhibited the activity of ML0314c. The protein was localized in cell wall and extracellular medium. Several antigenic epitopes were predicted in ML0314c. Protein elicited strong humoral immune response in leprosy patients, whereas, a reduced immune response was observed in the relapsed cases. No humoral response was observed in treatment completed patients. Overexpression of ml0314c in the surrogate host M. smegmatis showed marked difference in the colony morphology and growth rate. In conclusion, ML0314c is a secretary carboxyl esterase that could modulate the immune response in leprosy patients.
Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.
Mycobacterium leprae ML2603 similar to myctu-rv0183