Role of the lid hydrophobicity pattern in pancreatic lipase activity.
Identifieur interne : 000143 ( OpenAccess/Analysis ); précédent : 000142; suivant : 000144Role of the lid hydrophobicity pattern in pancreatic lipase activity.
Auteurs : Annick Thomas [Belgique] ; Maya Allouche ; Frédéric Basyn ; Robert Brasseur ; Brigitte KerfelecSource :
- The Journal of biological chemistry [ 0021-9258 ] ; 2005.
English descriptors
- KwdEn :
- Algorithms, Binding Sites, Catalysis, Dose-Response Relationship, Drug, Humans, Hydrogen-Ion Concentration, Hydrolysis, Kinetics, Lipase (chemistry), Lipase (metabolism), Models, Molecular, Models, Statistical, Mutation, Olive Oil, Pancreas (enzymology), Peptides (chemistry), Plant Oils, Plasmids (metabolism), Point Mutation, Protein Conformation, Protein Structure, Secondary, Triglycerides (chemistry).
- MESH :
- chemical , chemistry : Lipase, Peptides, Triglycerides.
- chemical , metabolism : Lipase.
- enzymology : Pancreas.
- metabolism : Plasmids.
- Algorithms, Binding Sites, Catalysis, Dose-Response Relationship, Drug, Humans, Hydrogen-Ion Concentration, Hydrolysis, Kinetics, Models, Molecular, Models, Statistical, Mutation, Olive Oil, Plant Oils, Point Mutation, Protein Conformation, Protein Structure, Secondary.
Abstract
Pancreatic lipase is a soluble globular protein that must undergo structural modifications before it can hydrolyze oil droplets coated with bile salts. The binding of colipase and movement of the lipase lid open access to the active site. Mechanisms triggering lid mobility are unclear. The *KNILSQIVDIDGI* fragment of the lid of the human pancreatic lipase is predicted by molecular modeling to be a tilted peptide. Tilted peptides are hydrophobicity motifs involved in membrane fusion and more globally in perturbations of hydrophobic/hydrophilic interfaces. Analysis of this lid fragment predicts no clear consensus of secondary structure that suggests that its structure is not strongly sequence determined and could vary with environment. Point mutations were designed to modify the hydrophobicity profile of the [240-252] fragment and their consequences on the lipase-mediated catalysis were tested. Two mutants, in which the tilted peptide motif was lost, also have poor activity on bile salt-coated oil droplets and cannot be reactivated by colipase. Conversely, one mutant in which a different tilted peptide is created retains colipase dependence. These results suggest that the tilted hydrophobicity pattern of the [240-252] fragment is neither important for colipase binding to lipase, nor for interfacial binding but is important to trigger the maximal catalytic efficiency of lipase in the presence of bile salt.
DOI: 10.1074/jbc.M502123200
PubMed: 16179352
Affiliations:
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pubmed:16179352Le document en format XML
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uniqKey="Brasseur R" first="Robert" last="Brasseur">Robert Brasseur</name></author><author><name sortKey="Kerfelec, Brigitte" sort="Kerfelec, Brigitte" uniqKey="Kerfelec B" first="Brigitte" last="Kerfelec">Brigitte Kerfelec</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2005">2005</date><idno type="RBID">pubmed:16179352</idno><idno type="pmid">16179352</idno><idno type="doi">10.1074/jbc.M502123200</idno><idno type="wicri:Area/PubMed/Corpus">000057</idno><idno type="wicri:Area/PubMed/Curation">000057</idno><idno type="wicri:Area/PubMed/Checkpoint">000057</idno><idno type="wicri:Area/Ncbi/Merge">000009</idno><idno type="wicri:Area/Ncbi/Curation">000009</idno><idno type="wicri:Area/Ncbi/Checkpoint">000009</idno><idno type="wicri:doubleKey">0021-9258:2005:Thomas A:role:of:the</idno><idno type="wicri:Area/Main/Merge">001715</idno><idno type="wicri:Area/Main/Curation">001706</idno><idno type="wicri:Area/Main/Exploration">001706</idno><idno 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Basyn</name></author><author><name sortKey="Brasseur, Robert" sort="Brasseur, Robert" uniqKey="Brasseur R" first="Robert" last="Brasseur">Robert Brasseur</name></author><author><name sortKey="Kerfelec, Brigitte" sort="Kerfelec, Brigitte" uniqKey="Kerfelec B" first="Brigitte" last="Kerfelec">Brigitte Kerfelec</name></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="ISSN">0021-9258</idno><imprint><date when="2005" type="published">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Algorithms</term><term>Binding Sites</term><term>Catalysis</term><term>Dose-Response Relationship, Drug</term><term>Humans</term><term>Hydrogen-Ion Concentration</term><term>Hydrolysis</term><term>Kinetics</term><term>Lipase (chemistry)</term><term>Lipase (metabolism)</term><term>Models, Molecular</term><term>Models, Statistical</term><term>Mutation</term><term>Olive Oil</term><term>Pancreas (enzymology)</term><term>Peptides (chemistry)</term><term>Plant Oils</term><term>Plasmids (metabolism)</term><term>Point Mutation</term><term>Protein Conformation</term><term>Protein Structure, Secondary</term><term>Triglycerides (chemistry)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Lipase</term><term>Peptides</term><term>Triglycerides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Lipase</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Pancreas</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Plasmids</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Algorithms</term><term>Binding Sites</term><term>Catalysis</term><term>Dose-Response Relationship, Drug</term><term>Humans</term><term>Hydrogen-Ion Concentration</term><term>Hydrolysis</term><term>Kinetics</term><term>Models, Molecular</term><term>Models, Statistical</term><term>Mutation</term><term>Olive Oil</term><term>Plant Oils</term><term>Point Mutation</term><term>Protein Conformation</term><term>Protein Structure, Secondary</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Pancreatic lipase is a soluble globular protein that must undergo structural modifications before it can hydrolyze oil droplets coated with bile salts. The binding of colipase and movement of the lipase lid open access to the active site. Mechanisms triggering lid mobility are unclear. The *KNILSQIVDIDGI* fragment of the lid of the human pancreatic lipase is predicted by molecular modeling to be a tilted peptide. Tilted peptides are hydrophobicity motifs involved in membrane fusion and more globally in perturbations of hydrophobic/hydrophilic interfaces. Analysis of this lid fragment predicts no clear consensus of secondary structure that suggests that its structure is not strongly sequence determined and could vary with environment. Point mutations were designed to modify the hydrophobicity profile of the [240-252] fragment and their consequences on the lipase-mediated catalysis were tested. Two mutants, in which the tilted peptide motif was lost, also have poor activity on bile salt-coated oil droplets and cannot be reactivated by colipase. Conversely, one mutant in which a different tilted peptide is created retains colipase dependence. These results suggest that the tilted hydrophobicity pattern of the [240-252] fragment is neither important for colipase binding to lipase, nor for interfacial binding but is important to trigger the maximal catalytic efficiency of lipase in the presence of bile salt.</div></front></TEI><affiliations><list><country><li>Belgique</li></country></list><tree><noCountry><name sortKey="Allouche, Maya" sort="Allouche, Maya" uniqKey="Allouche M" first="Maya" last="Allouche">Maya Allouche</name><name sortKey="Basyn, Frederic" sort="Basyn, Frederic" uniqKey="Basyn F" first="Frédéric" last="Basyn">Frédéric Basyn</name><name sortKey="Brasseur, Robert" sort="Brasseur, Robert" uniqKey="Brasseur R" first="Robert" last="Brasseur">Robert Brasseur</name><name sortKey="Kerfelec, Brigitte" sort="Kerfelec, Brigitte" uniqKey="Kerfelec B" first="Brigitte" last="Kerfelec">Brigitte Kerfelec</name></noCountry><country name="Belgique"><noRegion><name sortKey="Thomas, Annick" sort="Thomas, Annick" uniqKey="Thomas A" first="Annick" last="Thomas">Annick Thomas</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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