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Crystal structure of autotaxin and insight into GPCR activation by lipid mediators.

Nishimasu H, Okudaira S, Hama K, Mihara E, Dohmae N, Inoue A, Ishitani R, Takagi J, Aoki J, Nureki O
Nat Struct Mol Biol 18 205-12 (2011)
Related entries: 3nkm, 3nkn, 3nko, 3nkp, 3nkr

Cited: 136 times
EuropePMC logo PMID: 21240269

Abstract

Autotaxin (ATX, also known as Enpp2) is a secreted lysophospholipase D that hydrolyzes lysophosphatidylcholine to generate lysophosphatidic acid (LPA), a lipid mediator that activates G protein-coupled receptors to evoke various cellular responses. Here, we report the crystal structures of mouse ATX alone and in complex with LPAs with different acyl-chain lengths and saturations. These structures reveal that the multidomain architecture helps to maintain the structural rigidity of the lipid-binding pocket, which accommodates the respective LPA molecules in distinct conformations. They indicate that a loop region in the catalytic domain is a major determinant for the substrate specificity of the Enpp family enzymes. Furthermore, along with biochemical and biological data, these structures suggest that the produced LPAs are delivered from the active site to cognate G protein-coupled receptors through a hydrophobic channel.

Reviews - 3nkq mentioned but not cited (1)

  1. Cellular function and molecular structure of ecto-nucleotidases. Zimmermann H, Zebisch M, Sträter N. Purinergic Signal 8 437-502 (2012)

Articles - 3nkq mentioned but not cited (2)

  1. Target highlights in CASP9: Experimental target structures for the critical assessment of techniques for protein structure prediction. Kryshtafovych A, Moult J, Bartual SG, Bazan JF, Berman H, Casteel DE, Christodoulou E, Everett JK, Hausmann J, Heidebrecht T, Hills T, Hui R, Hunt JF, Seetharaman J, Joachimiak A, Kennedy MA, Kim C, Lingel A, Michalska K, Montelione GT, Otero JM, Perrakis A, Pizarro JC, van Raaij MJ, Ramelot TA, Rousseau F, Tong L, Wernimont AK, Young J, Schwede T. Proteins 79 Suppl 10 6-20 (2011)
  2. Computational identification and experimental characterization of substrate binding determinants of nucleotide pyrophosphatase/phosphodiesterase 7. Parrill AL, Wanjala IW, Pham TC, Baker DL. BMC Biochem 12 65 (2011)


Reviews citing this publication (43)

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Articles citing this publication (90)

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