Dridi_2013_Biochim.Biophys.Acta_1831_1293

Reference

Title : Partial deletion of beta9 loop in pancreatic lipase-related protein 2 reduces enzyme activity with a larger effect on long acyl chain substrates - Dridi_2013_Biochim.Biophys.Acta_1831_1293
Author(s) : Dridi K , Amara S , Bezzine S , Rodriguez JA , Carriere F , Gaussier H
Ref : Biochimica & Biophysica Acta , 1831 :1293 , 2013
Abstract :

Structural studies on pancreatic lipase have revealed a complex architecture of surface loops surrounding the enzyme active site and potentially involved in interactions with lipids. Two of them, the lid and beta loop, expose a large hydrophobic surface and are considered as acyl chain binding sites based on their interaction with an alkyl phosphonate inhibitor. While the role of the lid in substrate recognition and selectivity has been extensively studied, the implication of beta9 loop in acyl chain stabilization remained hypothetical. The characterization of an enzyme with a natural deletion of the lid, guinea pig pancreatic lipase-related protein 2 (GPLRP2), suggests however an essential contribution of the beta9 loop in the stabilization of the acyl enzyme intermediate formed during the lipolysis reaction. A GPLRP2 mutant with a seven-residue deletion of beta9 loop (GPLRP2-deltabeta9) was produced and its enzyme activity was measured using various substrates (triglycerides, monoglycerides, galactolipids, phospholipids, vinyl esters) with short, medium and long acyl chains. Whatever the substrate tested, GPLRP2-deltabeta9 activity is drastically reduced compared to that of wild-type GPLRP2 and this effect is more pronounced as the length of substrate acyl chain increases. Changes in relative substrate selectivity and stereoselectivity remained however weak. The deletion within beta9 loop has also a negative effect on the rate of enzyme inhibition by alkyl phosphonates. All these findings indicate that the reduced enzyme turnover observed with GPLRP2-deltabeta9 results from a weaker stabilization of the acyl enzyme intermediate due to a loss of hydrophobic interactions.

PubMedSearch : Dridi_2013_Biochim.Biophys.Acta_1831_1293
PubMedID: 24046870
Gene_locus related to this paper: human-PNLIPRP2

Related information

Gene_locus human-PNLIPRP2

Citations formats

Dridi K, Amara S, Bezzine S, Rodriguez JA, Carriere F, Gaussier H (2013)
Partial deletion of beta9 loop in pancreatic lipase-related protein 2 reduces enzyme activity with a larger effect on long acyl chain substrates
Biochimica & Biophysica Acta 1831 :1293

Dridi K, Amara S, Bezzine S, Rodriguez JA, Carriere F, Gaussier H (2013)
Biochimica & Biophysica Acta 1831 :1293