title: Molecular dynamics simulation of Autotaxin: roles of the nuclease-like domain and the glycan modification.
abstract: Autotaxin (ATX) is a secreted lysophospholipase D that produces lysophosphatidic acid, a lipid mediator that activates G protein-coupled receptors to evoke various cellular responses. The nuclease-like domain of ATX and the Asn524-linked glycan are reportedly critical for the catalytic activity. Recently, the crystal structures of ATX were determined, but the means by which the nuclease-like domain and the N-glycosylation participate in the catalytic activity still remain undetermined. To address this question, we conducted molecular dynamics simulations of ATX. The simulation trajectories starting from the full-length structure and from structures lacking the nuclease-like domain and/or the glycan were compared. The results suggested that an allosteric interaction pathway, formed by the catalytic domain, including the two insertion regions, the essential glycan modification, and the nuclease-like domain, may stabilize the proper location of the catalytic threonine residue. The results complement those from previous biochemical experiments.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Tokyo 113-0032, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Koyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishimasu
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Ishitani
authors.forename: Osamu
authors.initials: O
authors.lastname: Nureki
mesh_terms: D055162:Biocatalysis; D020134:Catalytic Domain; D004795:Enzyme Stability; D004950:Esterases / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D050356:Lipid Metabolism; D056004:Molecular Dynamics Simulation; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D000099189:Lysophospholipase D
chemical_list: D004950:Esterases; D010727:Phosphoric Diester Hydrolases; D011134:Polysaccharides; D000099189:Lysophospholipase D