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Nat Commun. 2016 Mar 11;7:10906. doi: 10.1038/ncomms10906.

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

Author information

1
Unidad de Biofísica, Consejo Superior de Investigaciones Científicas-Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU), Barrio Sarriena s/n, Leioa, 48940 Bizkaia, Spain.
2
Departamento de Bioquímica, Universidad del País Vasco, Leioa, 48940 Bizkaia, Spain.
3
IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain.
4
Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, 84215 Bratislava, Slovakia.
5
Université d'Orléans et CNRS, ICOA, UMR 7311, F-45067 Orléans, France.
6
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523-1682, USA.
7
Structural Biology Unit, CIC bioGUNE, Bizkaia Technology Park, 48160 Derio, Spain.

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.

PMID:
26965057
PMCID:
PMC4792965
DOI:
10.1038/ncomms10906
[Indexed for MEDLINE]
Free PMC Article

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