scholarly journals Solution and Membrane Interaction Dynamics of Mycobacterium tuberculosis Fatty Acyl-CoA Synthetase FadD13

Biochemistry ◽  
2021 ◽  
Author(s):  
Camilla A. K. Lundgren ◽  
Michael Lerche ◽  
Charlotta Norling ◽  
Martin Högbom
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Fatty Acyl ◽  
Membrane Interaction ◽  
Interaction Dynamics

Molecular Basis of the Functional Divergence of Fatty Acyl-AMP Ligase Biosynthetic Enzymes of Mycobacterium tuberculosis

2012 ◽  
Vol 416 (2) ◽  
pp. 221-238 ◽  
Author(s):  
Aneesh Goyal ◽  
Priyanka Verma ◽  
Madhankumar Anandhakrishnan ◽  
Rajesh S. Gokhale ◽  
Rajan Sankaranarayanan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Basis ◽  
Functional Divergence ◽  
Fatty Acyl ◽  
Biosynthetic Enzymes

scholarly journals Development of small-molecule inhibitors of fatty acyl-AMP and fatty acyl-CoA ligases in Mycobacterium tuberculosis

2020 ◽  
Vol 201 ◽  
pp. 112408 ◽  
Author(s):  
Marzena Baran ◽  
Kimberly D. Grimes ◽  
Paul A. Sibbald ◽  
Peng Fu ◽  
Helena I.M. Boshoff ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Fatty Acyl

scholarly journals Multiple-stage Precursor Ion Separation and High Resolution Mass Spectrometry toward Structural Characterization of 2,3-Diacyltrehalose Family from Mycobacterium tuberculosis

Separations ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. 4 ◽  
Author(s):  
Cheryl Frankfater ◽  
Robert Abramovitch ◽  
Georgiana Purdy ◽  
John Turk ◽  
Laurent Legentil ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mycobacterium Tuberculosis ◽  
High Resolution ◽  
Structural Characterization ◽  
High Resolution Mass Spectrometry ◽  
Complex Mixture ◽  
Fatty Acyl ◽  
High Resolution Mass ◽  
Resolution Mass

Mass spectrometry (MS)-based precursor ion isolation, collision-induced dissociation (CID) fragmentation, and detection using linear ion-trap multiple-stage mass spectrometry (LIT MSn) in combination with high resolution mass spectrometry (HRMS) provides a unique tool for structural characterization of complex mixture without chromatographic separation. This approach permits not only separation of various lipid families and their subfamilies, but also stereoisomers, thereby, revealing the structural details. In this report, we describe the LIT MSn approach to unveil the structures of a 2,3-diacyl trehalose (DAT) family isolated from the cell envelope of Mycobacterium tuberculosis, in which more than 30 molecular species, and each species consisting of up to six isomeric structures were found. LIT MSn performed on both [M + Na]+ and [M + HCO2]− ions of DAT yield complimentary structural information for near complete characterization of the molecules, including the location of the fatty acyl substituents on the trehalose backbone. This latter information is based on the findings of the differential losses of the two fatty acyl chains in the MS2 and MS3 spectra; while the product ion spectra from higher stage LIT MSn permit confirmation of the structural assignment.

scholarly journals Long-Chain Fatty Acyl Coenzyme A Ligase FadD2 Mediates Intrinsic Pyrazinamide Resistance in Mycobacterium tuberculosis

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Brandon C. Rosen ◽  
Nicholas A. Dillon ◽  
Nicholas D. Peterson ◽  
Yusuke Minato ◽  
Anthony D. Baughn
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Coenzyme A ◽  
Fatty Acyl ◽  
Wild Type ◽  
Intrinsic Resistance ◽  
First Line ◽  
Minimum Concentration ◽  
Content Type ◽  
Acyl Coenzyme A ◽  
Long Chain

ABSTRACT Pyrazinamide (PZA) is a first-line tuberculosis (TB) drug that has been in clinical use for 60 years yet still has an unresolved mechanism of action. Based upon the observation that the minimum concentration of PZA required to inhibit the growth of Mycobacterium tuberculosis is approximately 1,000-fold higher than that of other first-line drugs, we hypothesized that M. tuberculosis expresses factors that mediate intrinsic resistance to PZA. To identify genes associated with intrinsic PZA resistance, a library of transposon-mutagenized Mycobacterium bovis BCG strains was screened for strains showing hypersusceptibility to the active form of PZA, pyrazinoic acid (POA). Disruption of the long-chain fatty acyl coenzyme A (CoA) ligase FadD2 enhanced POA susceptibility by 16-fold on agar medium, and the wild-type level of susceptibility was restored upon expression of fadD2 from an integrating mycobacterial vector. Consistent with the recent observation that POA perturbs mycobacterial CoA metabolism, the fadD2 mutant strain was more vulnerable to POA-mediated CoA depletion than the wild-type strain. Ectopic expression of the M. tuberculosis pyrazinamidase PncA, necessary for conversion of PZA to POA, in the fadD2 transposon insertion mutant conferred at least a 16-fold increase in PZA susceptibility under active growth conditions in liquid culture at neutral pH. Importantly, deletion of fadD2 in M. tuberculosis strain H37Rv also resulted in enhanced susceptibility to POA. These results indicate that FadD2 is associated with intrinsic PZA and POA resistance and provide a proof of concept for the target-based potentiation of PZA activity in M. tuberculosis.

scholarly journals Fatty Acyl Structures of Mycobacterium tuberculosis Sulfoglycolipid Govern T Cell Response

2009 ◽  
Vol 182 (11) ◽  
pp. 7030-7037 ◽  
Author(s):  
Julie Guiard ◽  
Anthony Collmann ◽  
Luis Fernando Garcia-Alles ◽  
Lionel Mourey ◽  
Thérèse Brando ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Cell Response ◽  
Fatty Acyl ◽  
T Cell Response

scholarly journals Mycobacterium tuberculosis FasR senses long fatty acyl-CoA through a tunnel and a hydrophobic transmission spine

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Julia Lara ◽  
Lautaro Diacovich ◽  
Felipe Trajtenberg ◽  
Nicole Larrieux ◽  
Emilio L. Malchiodi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Fatty Acyl

Fatty acyl-AMP ligases and polyketide synthases are unique enzymes of lipid biosynthetic machinery in Mycobacterium tuberculosis

Tuberculosis ◽  
2011 ◽  
Vol 91 (5) ◽  
pp. 448-455 ◽  
Author(s):  
Debasisa Mohanty ◽  
Rajan Sankaranarayanan ◽  
Rajesh S. Gokhale
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Fatty Acyl ◽  
Polyketide Synthases ◽  
Biosynthetic Machinery
Sign in / Sign up

Export Citation Format

Share Document