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Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Structural Homologies, Importance for Catalysis and Lipid Binding of the N-Terminal Peptide of a Fungal and a Pancreatic Lipase

Author(s): Fakher Frikha, Nabil Miled, Abir Ben Bacha, Hafedh Mejdoub and Youssef Gargouri

Volume 17, Issue 2, 2010

Page: [254 - 259] Pages: 6

DOI: 10.2174/092986610790226049

Price: $65

Abstract

Lipases share an overall α/β hydrolase fold structure characteristic of serine hydrolases. Nevertheless, each lipases group possesses its characteristic 3-D structure and catalytic properties. The purified N-terminal truncated forms of a pancreatic (from ostrich) and a fungal (from Rhizopus oryzae, ROL32) (sayari et al., 2005) lipases displayed much lower activities as compared to the native proteins. The aim of this study is to explain this common functional feature on a structural basis. The molecular modelling showed that the N-terminal peptide of the fungal lipase displays an extended “V” shaped structure motif (sayari et al., 2005). We observed that the N-terminal peptide of a pancreatic lipase shares the same extended structure with that of the ROL32, despite the low sequence homology between the two peptides. Upon superimposition of the 3-D structure of the N-terminal catalytic domain of the pancreatic lipase with the model of the ROL32, we have shown that the N-terminal peptide and the open lid domain, of each lipase, are located distally within the putative interfacial binding surface. In particular, two hydrophobic residues, Leu and Ile belonging to the N-terminal peptide of each lipase are well placed to interact with the lipidic substrate. Furthermore, the N-terminal peptide of each lipase seems to be well placed to interact with the loop bearing the catalytic aspartic acid. All these observations might explain the fact that the loss of the N-terminal peptide affects the lipase activity. This work shows that the two lipases share striking structural and functional features with respect to their N-terminal peptide despite the fact that they belong to very distant kingdoms such as fungal and higher animals ones.

Keywords: Rhizopus oryzae lipase, pancreatic lipase, N-terminal peptide, homology modelling, structure, activity


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