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Molecular ruler mechanism and interfacial catalysis of the integral membrane acyltransferase PatA
Itxaso Anso
Luis GM Basso
Lei Wang
Alberto Marina
Edgar Daniel Páez Pérez
Christian Jäger
Floriane Gavotto
Montse Tersa
Sebastián Perrone
F-Xabier Contreras
Jacques Prandi
Martine GILLERON
Carole Linster
Francisco Corzana
Todd Lowary
Beatriz Trastoy
Marcelo Guerin
Acceso Abierto
Atribución-NoComercial-SinDerivadas
https://doi.org/10.1126/sciadv.abj4565
Bacillus-calmette guerin
Phosphatidylinositol mannosides
Mannosyltransferase pima
Enzymatic acylation
Structural basis
Lipid-bilayer
Biosynthesis
Mycobacteria
Recognition
Dynamics
"Glycolipids are prominent components of bacterial membranes that play critical roles not only in maintaining the structural integrity of the cell but also in modulating host-pathogen interactions. PatA is an essential acyltransferase involved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIMs), key structural elements and virulence factors of Mycobacterium tuberculosis. We demonstrate by electron spin resonance spectroscopy and surface plasmon resonance that PatA is an integral membrane acyltransferase tightly anchored to anionic lipid bilayers, using a two-helix structural motif and electrostatic interactions. PatA dictates the acyl chain composition of the glycolipid by using an acyl chain selectivity “ruler.” We established this by a combination of structural biology, enzymatic activity, and binding measurements on chemically synthesized nonhydrolyzable acyl–coenzyme A (CoA) derivatives. We propose an interfacial catalytic mechanism that allows PatA to acylate hydrophobic PIMs anchored in the inner membrane of mycobacteria, through the use of water-soluble acyl-CoA donors."
AAAS
2021
Artículo
Anso, I., Basso, L. G. M., Wang, L., Marina, A., Páez-Pérez, E. D., Jäger, C., … Guerin, M. E. (2021). Molecular ruler mechanism and interfacial catalysis of the integral membrane acyltransferase PatA. Science Advances, 7(42). https://doi.org/10.1126/sciadv.abj4565
CIENCIAS TECNOLÓGICAS
Aparece en las colecciones: Publicaciones Científicas Biología Molecular

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