title: The hydrolysis of lysophospholipids and nucleotides by autotaxin (NPP2) involves a single catalytic site.
abstract: Autotaxin (NPP2) is a tumor cell motility-stimulating factor that displays both a nucleotide pyrophosphatase/phosphodiesterase activity and a recently described lysophospholipase D activity. The hydrolysis of nucleotides is a metal-assisted reaction that occurs via a nucleotidylated threonine in the catalytic site. We show here that the catalytic site threonine and the metal-coordinating residues are also essential for the hydrolysis of lysophospholipids. In comparing the substrate specificity of NPP2 and the closely related NPP1 and NPP3, we found that only NPP2 displayed a lysophospholipase D activity, whereas NPP1 and NPP3 had a much higher nucleotide pyrophosphatase activity.
authors.affiliation: Afdeling Biochemie, Faculteit Geneeskunde, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Gijsbers
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bollen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D020134:Catalytic Domain; D004591:Electrophoresis, Polyacrylamide Gel; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D009097:Multienzyme Complexes; D009711:Nucleotides / Q000378:metabolism*; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D000099189:Lysophospholipase D
chemical_list: D005956:Glucose-6-Phosphate Isomerase; D006023:Glycoproteins; D008246:Lysophospholipids; D009097:Multienzyme Complexes; D009711:Nucleotides; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D000099189:Lysophospholipase D