Structural basis for selective recognition of acyl chains by the membrane-associated acyltransferase PatA

David Albesa-Jové, Zuzana Svetlíková, Montse Tersa, Enea Sancho-Vaello, Ana Carreras-González, Pascal Bonnet, Pedro Arrasate, Ander Eguskiza, Shiva K. Angala, Javier O. Cifuente, Jana Korduláková, Mary Jackson, Katarína Mikušová and Marcelo E. Guerin ()
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David Albesa-Jové: Unidad de Biofísica, Consejo Superior de Investigaciones Científicas—Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU), Barrio Sarriena s/n
Zuzana Svetlíková: Faculty of Natural Sciences, Comenius University in Bratislava
Montse Tersa: Unidad de Biofísica, Consejo Superior de Investigaciones Científicas—Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU), Barrio Sarriena s/n
Enea Sancho-Vaello: Unidad de Biofísica, Consejo Superior de Investigaciones Científicas—Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU), Barrio Sarriena s/n
Ana Carreras-González: Unidad de Biofísica, Consejo Superior de Investigaciones Científicas—Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU), Barrio Sarriena s/n
Pascal Bonnet: Université d’Orléans et CNRS, ICOA, UMR 7311
Pedro Arrasate: Unidad de Biofísica, Consejo Superior de Investigaciones Científicas—Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU), Barrio Sarriena s/n
Ander Eguskiza: Unidad de Biofísica, Consejo Superior de Investigaciones Científicas—Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU), Barrio Sarriena s/n
Shiva K. Angala: Mycobacteria Research Laboratories, Immunology and Pathology, Colorado State University
Javier O. Cifuente: Unidad de Biofísica, Consejo Superior de Investigaciones Científicas—Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU), Barrio Sarriena s/n
Jana Korduláková: Faculty of Natural Sciences, Comenius University in Bratislava
Mary Jackson: Mycobacteria Research Laboratories, Immunology and Pathology, Colorado State University
Katarína Mikušová: Faculty of Natural Sciences, Comenius University in Bratislava
Marcelo E. Guerin: Unidad de Biofísica, Consejo Superior de Investigaciones Científicas—Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU), Barrio Sarriena s/n

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract The biosynthesis of phospholipids and glycolipids are critical pathways for virtually all cell membranes. PatA is an essential membrane associated acyltransferase involved in the biosynthesis of mycobacterial phosphatidyl-myo-inositol mannosides (PIMs). The enzyme transfers a palmitoyl moiety from palmitoyl–CoA to the 6-position of the mannose ring linked to 2-position of inositol in PIM1/PIM2. We report here the crystal structures of PatA from Mycobacterium smegmatis in the presence of its naturally occurring acyl donor palmitate and a nonhydrolyzable palmitoyl–CoA analog. The structures reveal an α/β architecture, with the acyl chain deeply buried into a hydrophobic pocket that runs perpendicular to a long groove where the active site is located. Enzyme catalysis is mediated by an unprecedented charge relay system, which markedly diverges from the canonical HX4D motif. Our studies establish the mechanistic basis of substrate/membrane recognition and catalysis for an important family of acyltransferases, providing exciting possibilities for inhibitor design.

Date: 2016
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DOI: 10.1038/ncomms10906

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