title: Differential spontaneous folding of mycolic acids from Mycobacterium tuberculosis.
abstract: Mycolic acids are structural components of the mycobacterial cell wall that have been implicated in the pathogenicity and drug resistance of certain mycobacterial species. They also offer potential in areas such as rapid serodiagnosis of human and animal tuberculosis. It is increasingly recognized that conformational behavior of mycolic acids is very important in understanding all aspects of their function. Atomistic molecular dynamics simulations, in vacuo, of stereochemically defined Mycobacterium tuberculosis mycolic acids show that they fold spontaneously into reproducible conformational groupings. One of the three characteristic mycolate types, the keto-mycolic acids, behaves very differently from either α-mycolic acids or methoxy-mycolic acids, suggesting a distinct biological role. However, subtle conformational behavioral differences between all the three mycolic acid types indicate that cooperative interplay of individual mycolic acids may be important in the biophysical properties of the mycobacterial cell envelope and therefore in pathogenicity.
authors.affiliation: Department of Biochemistry, University of Pretoria, Pretoria 0002, South Africa; School of Chemistry, University of Wales Bangor, Bangor LL57 2UW, UK.
authors.forename: Wilma
authors.initials: W
authors.lastname: Groenewald
authors.affiliation: School of Chemistry, University of Wales Bangor, Bangor LL57 2UW, UK.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Baird
authors.affiliation: Department of Biochemistry, University of Pretoria, Pretoria 0002, South Africa.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Verschoor
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Minnikin
authors.affiliation: School of Chemistry, University of Wales Bangor, Bangor LL57 2UW, UK; Department of Chemical and Environmental Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK. Electronic address: anna.croft@nottingham.ac.uk.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Croft
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009169:Mycobacterium tuberculosis; D009171:Mycolic Acids / Q000737:chemistry*; D025341:Principal Component Analysis; D013499:Surface Properties; D013816:Thermodynamics
chemical_list: D009171:Mycolic Acids
keywords: Folding; Molecular dynamics; Mycobacterium tuberculosis; Mycolic acid; Principle component analysis