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

DOI: 10.1038/ncomms10906 DOI Help

Authors: David Albesa-jove (Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU)) , Zuzana Svetlíková (Comenius University in Bratislava) , Montse Tersa (Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU)) , Enea Sancho-vaello (Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU)) , Ana Carreras-gonzález (Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU)) , Pascal Bonnet (Université d’Orléans et CNRS) , Pedro Arrasate (Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU)) , Ander Eguskiza (Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU)) , Shiva K. Angala (Colorado State University) , Javier Orlando Cifuente (Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU)) , Jana Korduláková (Comenius University in Bratislava) , Mary Jackson (Colorado State University) , Katarína Mikušová (Comenius University in Bratislava) , Marcelo Guerin (Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 7

State: Published (Approved)
Published: March 2016

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.

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography