title: Conformational folding of mycobacterial methoxy- and ketomycolic acids facilitated by α-methyl trans-cyclopropane groups rather than cis-cyclopropane units.
abstract: The oxygenated long-chain mycolic acids from many mycobacteria are characterized by the presence of mid-chain cyclopropane groups, which can have either cis-configuration or trans-configuration with an adjacent methyl branch. To determine the effect of these functional groups on mycolic acid conformation, surface pressure (π) versus mean molecular area isotherms of methoxy- (MeO-) mycolic acids (MAs) from Mycobacterium kansasii, Mycobacterium tuberculosis (Mtb) Canetti and Mtb H37Ra, and of keto-MAs from Mycobacterium avium-intracellulare complex (MAC) and Mtb H37Ra were recorded and analysed. The MeO- and keto-MAs from Mtb H37Ra, containing scarcely any trans-cyclopropyl groups, apparently took no fully folded 'W-form' conformations. Keto-MA from MAC, whose trans-cyclopropyl group content is nearly 90 %, showed a very solid W-form conformation. MeO-MAs from M. kansasii and Mtb Canetti gave stable W-form conformations at lower temperatures and surface pressures and extended conformations at higher temperatures and surface pressures; their W-form conformation was not as stable as expected from their cis-cyclopropyl group content, probably because they had a wide range of constituent homologues. Energy level calculations of cis- or α-methyl trans-cyclopropane-containing model molecules and computer simulation studies confirmed the superior folding properties of the latter functional unit. The present results were compared with those of MeO- and keto-MAs from Mtb and from M. bovis Bacillus Calmette-Guérin (BCG) reported previously. Among the oxygenated MAs, those having higher trans-cyclopropane content tended to take W-form conformations more firmly, implying that the meromycolate proximal intra-chain α-methyl trans-cyclopropane groups facilitated MA folding more than cis-cyclopropane groups.
authors.affiliation: Division of Material Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama 338-8570, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Villeneuve
authors.affiliation: Division of Material Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama 338-8570, Japan.
authors.forename: Mizuo
authors.initials: M
authors.lastname: Kawai
authors.affiliation: Division of Material Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama 338-8570, Japan.
authors.forename: Kieko
authors.initials: K
authors.lastname: Horiuchi
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoyagi
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hitotsuyanagi
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeya
authors.affiliation: Faculty of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Gouda
authors.affiliation: Faculty of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hirono
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Minnikin
mesh_terms: D003198:Computer Simulation; D008968:Molecular Conformation; D015269:Mycobacterium avium Complex / Q000737:chemistry*; D019909:Mycobacterium kansasii / Q000737:chemistry*; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D009171:Mycolic Acids / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D009171:Mycolic Acids