A chemical reporter strategy for detecting and identifying O-mycoloylated proteins in Corynebacterium

2016 ◽  
Vol 52 (95) ◽  
pp. 13795-13798 ◽  
Author(s):  
Herbert W. Kavunja ◽  
Brent F. Piligian ◽  
Taylor J. Fiolek ◽  
Hannah N. Foley ◽  
Temitope O. Nathan ◽  
...  
Keyword(s):  
Chemical Reporter ◽  
Trehalose Monomycolate

A trehalose monomycolate (TMM)-mimicking chemical reporter facilitated the investigation of a recently discovered class of lipidated proteins in the Corynebacterineae.

scholarly journals Diazo group as a new chemical reporter for bioorthogonal labelling of biomolecules

RSC Advances ◽  
2014 ◽  
Vol 4 (94) ◽  
pp. 52241-52244 ◽  
Author(s):  
Laia Josa-Culleré ◽  
Yelena A. Wainman ◽  
Kevin M. Brindle ◽  
Finian J. Leeper
Keyword(s):  
Chemical Reporter ◽  
Strained Alkenes ◽  
Diazo Group

Diazoacetyl groups undergo spontaneous cycloaddition with strained alkenes and alkynes and can be bioorthogonal reporter groups labelling proteins and glycans.

scholarly journals The crystal structure of the mycobacterial trehalose monomycolate transport factor A, TtfA, reveals an atypical fold

2019 ◽  
Vol 88 (6) ◽  
pp. 809-815 ◽  
Author(s):  
Kien Lam Ung ◽  
Husam M. A. B. Alsarraf ◽  
Laurent Kremer ◽  
Mickaël Blaise
Keyword(s):  
Crystal Structure ◽  
Transport Factor ◽  
Trehalose Monomycolate

scholarly journals MmpL3 is a lipid transporter that binds trehalose monomycolate and phosphatidylethanolamine

2019 ◽  
Vol 116 (23) ◽  
pp. 11241-11246 ◽  
Author(s):  
Chih-Chia Su ◽  
Philip A. Klenotic ◽  
Jani Reddy Bolla ◽  
Georgiana E. Purdy ◽  
Carol V. Robinson ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cell Envelope ◽  
Native Mass Spectrometry ◽  
Mycolic Acids ◽  
Mycobacterial Cell ◽  
Exact Function ◽  
Species Specific ◽  
Mycobacterial Cell Wall ◽  
Trehalose Monomycolate ◽  
Lipid Transporter

The cell envelope ofMycobacterium tuberculosisis notable for the abundance of mycolic acids (MAs), essential to mycobacterial viability, and of other species-specific lipids. The mycobacterial cell envelope is extremely hydrophobic, which contributes to virulence and antibiotic resistance. However, exactly how fatty acids and lipidic elements are transported across the cell envelope for cell-wall biosynthesis is unclear. Mycobacterial membrane protein Large 3 (MmpL3) is essential and required for transport of trehalose monomycolates (TMMs), precursors of MA-containing trehalose dimycolates (TDM) and mycolyl arabinogalactan peptidoglycan, but the exact function of MmpL3 remains elusive. Here, we report a crystal structure ofMycobacterium smegmatisMmpL3 at a resolution of 2.59 Å, revealing a monomeric molecule that is structurally distinct from all known bacterial membrane proteins. A previously unknown MmpL3 ligand, phosphatidylethanolamine (PE), was discovered inside this transporter. We also show, via native mass spectrometry, that MmpL3 specifically binds both TMM and PE, but not TDM, in the micromolar range. These observations provide insight into the function of MmpL3 and suggest a possible role for this protein in shuttling a variety of lipids to strengthen the mycobacterial cell wall.

Syntheses of Trehalose Monomycolate and Related Compounds, and Their Lethal Toxicity and Adjuvant Activity

1986 ◽  
Vol 5 (1) ◽  
pp. 127-138 ◽  
Author(s):  
Fumio Numata ◽  
Hideharu Ishida ◽  
Keiko Nishimura ◽  
Isao Sekikawa ◽  
Ichiro Azuma
Keyword(s):  
Adjuvant Activity ◽  
Lethal Toxicity ◽  
Trehalose Monomycolate ◽  
Related Compounds

scholarly journals A bioorthogonal chemical reporter for fatty acid synthase-dependent protein acylation

2021 ◽  
pp. 101272
Author(s):  
Krithika P. Karthigeyan ◽  
Lizhi Zhang ◽  
David R. Loiselle ◽  
Timothy A.J. Haystead ◽  
Menakshi Bhat ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Chemical Reporter ◽  
Dependent Protein ◽  
Protein Acylation

scholarly journals The Metabolic Chemical Reporter Ac46AzGal Could Incorporate Intracellular Protein Modification in the Form of UDP-6AzGlc Mediated by OGT and Enzymes in the Leloir Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Jiajia Wang ◽  
Biao Dou ◽  
Lu Zheng ◽  
Wei Cao ◽  
Peiyu Dong ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Protein Modification ◽  
Time Dependent ◽  
Dependent Manner ◽  
Intracellular Protein ◽  
Galactose Metabolism ◽  
Naturally Occurring ◽  
Leloir Pathway ◽  
Chemical Reporter ◽  
Complex Glycans

Galactose is a naturally occurring monosaccharide used to build complex glycans that has not been targeted for labeling as a metabolic reporter. Here, we characterize the cellular modification of proteins by using Ac46AzGal in a dose- and time-dependent manner. It is noted that a vast majority of this labeling of Ac46AzGal occurs intracellularly in a range of mammalian cells. We also provided evidence that this labeling is dependent on not only the enzymes of OGT responsible for O-GlcNAcylation but also the enzymes of GALT and GALE in the Leloir pathway. Notably, we discover that Ac46AzGal is not the direct substrate of OGT, and the labeling results may attribute to UDP-6AzGlc after epimerization of UDP-6AzGal via GALE. Together, these discoveries support the conclusion that Ac46AzGal as an analogue of galactose could metabolically label intracellular O-glycosylation modification, raising the possibility of characterization with impaired functions of the galactose metabolism in the Leloir pathway under certain conditions, such as galactosemias.

scholarly journals Collagen labelling with an azide-proline chemical reporter in live cells

2015 ◽  
Vol 51 (25) ◽  
pp. 5250-5252 ◽  
Author(s):  
Beatrice Amgarten ◽  
Rakesh Rajan ◽  
Nuria Martínez-Sáez ◽  
Bruno L. Oliveira ◽  
Inês S. Albuquerque ◽  
...  
Keyword(s):  
Cycloaddition Reaction ◽  
Live Cells ◽  
Chemical Reporter

Biosynthetic incorporation of an azide-proline chemical reporter into collagen allows selective imaging in live foetal ovine osteoblasts using a strain-promoted [3+2] azide–alkyne cycloaddition reaction.

scholarly journals Pathway to Synthesis and Processing of Mycolic Acids in Mycobacterium tuberculosis

2005 ◽  
Vol 18 (1) ◽  
pp. 81-101 ◽  
Author(s):  
Kuni Takayama ◽  
Cindy Wang ◽  
Gurdyal S. Besra
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Fatty Acid ◽  
Candidate Genes ◽  
Abc Transporter ◽  
Polyketide Synthase ◽  
Acyl Carrier Protein ◽  
Fatty Acid Synthetase ◽  
Mycolic Acids ◽  
Trehalose Dimycolate ◽  
Trehalose Monomycolate

SUMMARY Mycobacterium tuberculosis is known to synthesize α-, methoxy-, and keto-mycolic acids. We propose a detailed pathway to the biosynthesis of all mycolic acids in M. tuberculosis. Fatty acid synthetase I provides C20-S-coenzyme A to the fatty acid synthetase II system (FAS-IIA). Modules of FAS-IIA and FAS-IIB introduce cis unsaturation at two locations on a growing meroacid chain to yield three different forms of cis,cis-diunsaturated fatty acids (intermediates to α-, methoxy-, and keto-meroacids). These are methylated, and the mature meroacids and carboxylated C26-S-acyl carrier protein enter into the final Claisen-type condensation with polyketide synthase-13 (Pks13) to yield mycolyl-S-Pks13. We list candidate genes in the genome encoding the proposed dehydrase and isomerase in the FAS-IIA and FAS-IIB modules. We propose that the processing of mycolic acids begins by transfer of mycolic acids from mycolyl-S-Pks13 to d-mannopyranosyl-1-phosphoheptaprenol to yield 6-O-mycolyl-β-d-mannopyranosyl-1-phosphoheptaprenol and then to trehalose 6-phosphate to yield phosphorylated trehalose monomycolate (TMM-P). Phosphatase releases the phosphate group to yield TMM, which is immediately transported outside the cell by the ABC transporter. Antigen 85 then catalyzes the transfer of a mycolyl group from TMM to the cell wall arabinogalactan and to other TMMs to produce arabinogalactan-mycolate and trehalose dimycolate, respectively. We list candidate genes in the genome that encode the proposed mycolyltransferases I and II, phosphatase, and ABC transporter. The enzymes within this total pathway are targets for new drug discovery.

scholarly journals Abnormal accumulation and recycling of glycoproteins visualized in Niemann-Pick type C cells using the chemical reporter strategy

2013 ◽  
Vol 110 (25) ◽  
pp. 10207-10212 ◽  
Author(s):  
N. E. Mbua ◽  
H. Flanagan-Steet ◽  
S. Johnson ◽  
M. A. Wolfert ◽  
G.-J. Boons ◽  
...  
Keyword(s):  
C Cells ◽  
Abnormal Accumulation ◽  
Chemical Reporter ◽  
Type C ◽  
Niemann Pick

First access to a mycolic acid-based bioorthogonal reporter for the study of the mycomembrane and mycoloyltransferases in Corynebacteria

2019 ◽  
Vol 55 (87) ◽  
pp. 13074-13077
Author(s):  
Emilie Lesur ◽  
Aurélie Baron ◽  
Christiane Dietrich ◽  
Marie Buchotte ◽  
Gilles Doisneau ◽  
...  
Keyword(s):  
Mycolic Acid ◽  
Complex Pattern ◽  
Mycolic Acids ◽  
Trehalose Monomycolate

In this study we describe the first synthesis of an alkyne-based trehalose monomycolate probe closely mimicking the complex pattern of mycolic acids and its utility for the study of mycomembrane and mycoloyltransferases in Corynebacteria.

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