The hydrolysis of lysophospholipids and nucleotides by autotaxin (NPP2) involves a single catalytic site

FEBS Letters

Arai, Hiroyuki¹  Bollen, Mathieu²  Gijsbers, Rik²  Aoki, Junken¹ 

[1] Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;Afdeling Biochemie, Faculteit Geneeskunde, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium

关键词: NPP;    Nucleotide pyrophosphatase/phosphodiesterase;    Lysophospholipase D;    Autotaxin;    Cell motility;    Catalytic mechanism;    PC-1;    NPP;    nucleotide pyrophosphatase/phosphodiesterase;    pNPP;    p-nitrophenylphosphate;    bis-pNPP;    bis(p-nitrophenyl)phosphate;    pNP-TMP;    p-nitrophenyl thymidine 5′-monophosphate;    lysoPC;    lysophosphatidylcholine;    lysoPA;    lysophosphatidic acid;   

DOI  :  10.1016/S0014-5793(03)00133-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown