HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, Y. Articles by Lowe, M. E. Search for Related Content PubMed PubMed Citation Articles by Yang, Y. Articles by Lowe, M. E. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 41, 48-57, January 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

The open lid mediates pancreatic lipase function

Correspondence to: Mark E. Lowe

Pancreatic triglyceride lipase (PTL) and the homologous pancreatic lipase related protein 2 (PLRP2) provide a unique opportunity to understand the molecular mechanism of lipolysis. They differ in substrate specificity, sensitivity to bile salts, and colipase dependence despite their close amino acid and tertiary structure identity. One important structure, present in both lipases, is the lid which occupies different positions in the inactive and active forms of PTL. We investigated the role of the lid in lipase function by site-specific mutagenesis. By exchanging the lids between PTL and PLRP2, we created two chimeric lipases. Additionally, we made multiple substitution mutations in the PTL lid. PLRP2 with the PTL lid had kinetic properties similar to PLRP2. PTL with the PLRP2 lid was greatly impaired and had no activity at micellar bile salt concentrations even in the presence of colipase. Both chimeras showed interfacial activation suggesting that the closed lid position was maintained. A series of substitution mutations were made in positions Arg257 and Asp258.

These mutations demonstrated the importance of these two residues to maintaining the normal activity, triglyceride acyl chain specificity, and colipase interaction of PTL. The preserved interfacial activation in the chimeras, the similar crystal structure of the two lids in the closed position, and the importance of Arg257 and Asp258 in mediating the open conformation of the lid argue that the position of the open lid influences the differences in activity against triglycerides, in sensitivity to bile salts, and in colipase dependence between PTL and PLRP2.—Yang, Y., and M. E. Lowe. The open lid mediates pancreatic lipase function. J. Lipid Res. 2000. 41: 48;–57.

Supplementary key words: pancreatic lipase-related protein, colipase, site-directed mutagenesis, bile salts

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Bourbon-Freie, R. E. Dub, X. Xiao, and M. E. Lowe Trp-107 and Trp-253 Account for the Increased Steady State Fluorescence That Accompanies the Conformational Change in Human Pancreatic Triglyceride Lipase Induced by Tetrahydrolipstatin and Bile Salt J. Biol. Chem., May 22, 2009; 284(21): 14157 - 14164. [Abstract] [Full Text] [PDF]

				A. Thomas, M. Allouche, F. Basyn, R. Brasseur, and B. Kerfelec Role of the Lid Hydrophobicity Pattern in Pancreatic Lipase Activity J. Biol. Chem., December 2, 2005; 280(48): 40074 - 40083. [Abstract] [Full Text] [PDF]

				M. E. Lowe The triglyceride lipases of the pancreas J. Lipid Res., December 1, 2002; 43(12): 2007 - 2016. [Abstract] [Full Text] [PDF]

				S. Y. Choi, K.-i. Hirata, T. Ishida, T. Quertermous, and A. D. Cooper Endothelial lipase: a new lipase on the block J. Lipid Res., November 1, 2002; 43(11): 1763 - 1769. [Abstract] [Full Text] [PDF]

				J. T. Mahan, G. D. Heda, R. H. Rao, and C. M. Mansbach II The intestine expresses pancreatic triacylglycerol lipase: regulation by dietary lipid Am J Physiol Gastrointest Liver Physiol, June 1, 2001; 280(6): G1187 - G1196. [Abstract] [Full Text] [PDF]