Structure Report for: 3U0V

Burger, M., Zimmermann, T.J., Kondoh, Y., Stege, P., Watanabe, N., Osada, H., Waldmann, H., Vetter, I.R.

Title: Crystal structure of the predicted phospholipase LYPLAL1 reveals unexpected functional plasticity despite close relationship to acyl protein thioesterases
Burger M, Zimmermann TJ, Kondoh Y, Stege P, Watanabe N, Osada H, Waldmann H, Vetter IR
Ref: J Lipid Res, 53:43, 2012 : PubMed
Abstract


ESTHER: Burger_2012_J.Lipid.Res_53_43
PubMedSearch: Burger 2012 J.Lipid.Res 53 43
PubMedID: 22052940
Gene_locus related to this paper: human-LYPLAL1

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 A 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.