5f34 › Citations

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

Albesa-Jové D, Svetlíková Z, Tersa M, Sancho-Vaello E, Carreras-González A, Bonnet P, Arrasate P, Eguskiza A, Angala SK, Cifuente JO, Korduláková J, Jackson M, Mikušová K, Guerin ME
Nat Commun 7 10906 (2016)
Related entries: 5f2t, 5f2z, 5f31

Cited: 19 times
EuropePMC logo PMID: 26965057

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.

Reviews - 5f34 mentioned but not cited (1)

  1. How lipid droplets "TAG" along: Glycerolipid synthetic enzymes and lipid storage. Wang H, Airola MV, Reue K. Biochim Biophys Acta Mol Cell Biol Lipids 1862 1131-1145 (2017)

Articles - 5f34 mentioned but not cited (4)

  1. Structural basis for selective recognition of acyl chains by the membrane-associated acyltransferase PatA. Albesa-Jové D, Svetlíková Z, Tersa M, Sancho-Vaello E, Carreras-González A, Bonnet P, Arrasate P, Eguskiza A, Angala SK, Cifuente JO, Korduláková J, Jackson M, Mikušová K, Guerin ME. Nat Commun 7 10906 (2016)
  2. Rickettsia Lipid A Biosynthesis Utilizes the Late Acyltransferase LpxJ for Secondary Fatty Acid Addition. Guillotte ML, Gillespie JJ, Chandler CE, Rahman MS, Ernst RK, Azad AF. J Bacteriol 200 e00334-18 (2018)
  3. Molecular ruler mechanism and interfacial catalysis of the integral membrane acyltransferase PatA. Anso I, Basso LGM, Wang L, Marina A, Páez-Pérez ED, Jäger C, Gavotto F, Tersa M, Perrone S, Contreras FX, Prandi J, Gilleron M, Linster CL, Corzana F, Lowary TL, Trastoy B, Guerin ME. Sci Adv 7 eabj4565 (2021)
  4. A dedicated C-6 β-hydroxyacyltransferase required for biosynthesis of the glycolipid anchor for Vi antigen capsule in typhoidal Salmonella. Liston SD, Ovchinnikova OG, Kimber MS, Whitfield C. J Biol Chem 298 102520 (2022)


Reviews citing this publication (1)

  1. The thick waxy coat of mycobacteria, a protective layer against antibiotics and the host's immune system. Batt SM, Minnikin DE, Besra GS. Biochem J 477 1983-2006 (2020)

Articles citing this publication (13)

  1. A two-helix motif positions the lysophosphatidic acid acyltransferase active site for catalysis within the membrane bilayer. Robertson RM, Yao J, Gajewski S, Kumar G, Martin EW, Rock CO, White SW. Nat Struct Mol Biol 24 666-671 (2017)
  2. Spatial control of cell envelope biosynthesis in mycobacteria. Puffal J, García-Heredia A, Rahlwes KC, Siegrist MS, Morita YS. Pathog Dis 76 (2018)
  3. N-Acetylglucosamine-1-Phosphate Transferase, WecA, as a Validated Drug Target in Mycobacterium tuberculosis. Huszár S, Singh V, Polčicová A, Baráth P, Barrio MB, Lagrange S, Leblanc V, Nacy CA, Mizrahi V, Mikušová K. Antimicrob Agents Chemother 61 e01310-17 (2017)
  4. Deletion of PimE mannosyltransferase results in increased copper sensitivity in Mycobacterium smegmatis. Eagen WJ, Baumoel LR, Osman SH, Rahlwes KC, Morita YS. FEMS Microbiol Lett 365 (2018)
  5. Structural basis for lipid binding and mechanism of the Mycobacterium tuberculosis Rv3802 phospholipase. Goins CM, Schreidah CM, Dajnowicz S, Ronning DR. J Biol Chem 293 1363-1372 (2018)
  6. The Phosphatidyl-myo-Inositol Dimannoside Acyltransferase PatA Is Essential for Mycobacterium tuberculosis Growth In Vitro and In Vivo. Boldrin F, Anso I, Alebouyeh S, Sevilla IA, Geijo M, Garrido JM, Marina A, Cioetto Mazzabò L, Segafreddo G, Guerin ME, Manganelli R, Prados-Rosales R. J Bacteriol 203 e00439-20 (2021)
  7. Cloning, Characterization, and Expression Analysis of a Gene Encoding a Putative Lysophosphatidic Acid Acyltransferase from Seeds of Paeonia rockii. Zhang QY, Niu LX, Yu R, Zhang XX, Bai ZZ, Duan K, Gao QH, Zhang YL. Appl Biochem Biotechnol 182 721-741 (2017)
  8. Transcriptional signatures of Mycobacterium tuberculosis in mouse model of intraocular tuberculosis. Abhishek S, Ryndak MB, Choudhary A, Sharma S, Gupta A, Gupta V, Singh N, Laal S, Verma I. Pathog Dis 77 ftz045 (2019)
  9. The Two-Component Locus MSMEG_0244/0246 Together With MSMEG_0243 Affects Biofilm Assembly in M. smegmatis Correlating With Changes in Phosphatidylinositol Mannosides Acylation. Li M, Gašparovič H, Weng X, Chen S, Korduláková J, Jessen-Trefzer C. Front Microbiol 11 570606 (2020)
  10. Mycobacterium avium subsp. paratuberculosis (Map) Fatty Acids Profile Is Strain-Dependent and Changes Upon Host Macrophages Infection. Alonso-Hearn M, Abendaño N, Ruvira MA, Aznar R, Landin M, Juste RA. Front Cell Infect Microbiol 7 89 (2017)
  11. Acylation of glycerolipids in mycobacteria. Angala SK, Carreras-Gonzalez A, Huc-Claustre E, Anso I, Kaur D, Jones V, Palčeková Z, Belardinelli JM, de Sousa-d'Auria C, Shi L, Slama N, Houssin C, Quémard A, McNeil M, Guerin ME, Jackson M. Nat Commun 14 6694 (2023)
  12. Bioinformatics Analysis to Uncover the Potential Drug Targets Responsible for Mycobacterium tuberculosis Peptidoglycan and Lysine Biosynthesis. Ayu Eka Pitaloka D, Izzati A, Rafa Amirah S, Abdan Syakuran L, Muhammad Irham L, Darumas Putri A, Adikusuma W. Bioinform Biol Insights 17 11779322231171774 (2023)
  13. PatA Regulates Isoniazid Resistance by Mediating Mycolic Acid Synthesis and Controls Biofilm Formation by Affecting Lipid Synthesis in Mycobacteria. Wang K, Deng Y, Cui X, Chen M, Ou Y, Li D, Guo M, Li W. Microbiol Spectr 11 e0092823 (2023)


Quick links