title: Crystal structure of the predicted phospholipase LYPLAL1 reveals unexpected functional plasticity despite close relationship to acyl protein thioesterases.
abstract: Sequence homology indicates the existence of three human cytosolic acyl protein thioesterases, including APT1 that is known to depalmitoylate H- and N-Ras. One of them is the lysophospholipase-like 1 (LYPLAL1) protein that on the one hand is predicted to be closely related to APT1 but on the other hand might also function as a potential triacylglycerol lipase involved in obesity. However, its role remained unclear. The 1.7 Å crystal structure of LYPLAL1 reveals a fold very similar to APT1, as expected, but features a shape of the active site that precludes binding of long-chain substrates. Biochemical data demonstrate that LYPLAL1 exhibits neither phospholipase nor triacylglycerol lipase activity, but rather accepts short-chain substrates. Furthermore, extensive screening efforts using chemical array technique revealed a first small molecule inhibitor of LYPLAL1.
authors: Department of Mechanistic Cell Biology,  Max Planck Institute of Molecular Physiology, Dortmund,  Germany.
authors: Marco
authors: M
authors: Bürger
authors: Tobias J
authors: TJ
authors: Zimmermann
authors: Yasumitsu
authors: Y
authors: Kondoh
authors: Patricia
authors: P
authors: Stege
authors: Nobumoto
authors: N
authors: Watanabe
authors: Hiroyuki
authors: H
authors: Osada
authors: Herbert
authors: H
authors: Waldmann
authors: Ingrid R
authors: IR
authors: Vetter
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D008049:Lipase / Q000378:metabolism; D008245:Lysophospholipase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010740:Phospholipases / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D010740:Phospholipases; D008049:Lipase; D008245:Lysophospholipase; C561408:LYPLAL1 protein, human