Abstract
The 3D structure of pancreatic lipase (PL) consists of two functional domains. The N-terminal domain belongs to the α/β hydrolase fold and contains the active site, which involves a catalytic triad analogous to that present in serine proteases. The β-sandwich C-terminal domain of PL plays an important part in the binding process between the lipase and colipase, the specific PL cofactor. Recent structure-function studies have suggested that the PL C-terminal domain may have an extra role apart from that of binding colipase. This domain contains an exposed hydrophobic loop (β5) which was found to be located on the same side as the hydrophobic loops surrounding the active site, and it may be involved in the lipid binding process. Indirect evidence for this new function of the PL C-terminal domain has been provided by studies with monoclonal antibodies directed against the β5 loop. The catalytic activity of the PL-antibody complexes on water insoluble substrates decreased drastically, whereas their esterase activity on a soluble substrate remained unchanged. During the last few years, a number of protein structures (15-lipoxygenase, a-toxin from Clostridium perfringens) have been determined that contain domains with close structural homologies with the β- sandwich C-terminal domain of PL. Generally speaking, these domains show structural homologies with the C2 domains occurring in a wide range of proteins involved in signal transduction (e.g. phosphoinositide-specific phospholipase C, protein kinase C, cytosolic phospholipase A2), membrane traffic (e.g. synaptotagmin I, rabphilin) and membrane disruption (e.g. perforin). Here it is proposed to review the structure and function of the C2 domains, based on the recent 3D structures and improved sequence alignments.
Current Protein & Peptide Science
Title: The C-Terminal Domain of Pancreatic Lipase: Functional and Structural Analogies with C2 Domains
Volume: 1 Issue: 1
Author(s): Chahinian H., Sias B. and Carriere F.
Affiliation:
Abstract: The 3D structure of pancreatic lipase (PL) consists of two functional domains. The N-terminal domain belongs to the α/β hydrolase fold and contains the active site, which involves a catalytic triad analogous to that present in serine proteases. The β-sandwich C-terminal domain of PL plays an important part in the binding process between the lipase and colipase, the specific PL cofactor. Recent structure-function studies have suggested that the PL C-terminal domain may have an extra role apart from that of binding colipase. This domain contains an exposed hydrophobic loop (β5) which was found to be located on the same side as the hydrophobic loops surrounding the active site, and it may be involved in the lipid binding process. Indirect evidence for this new function of the PL C-terminal domain has been provided by studies with monoclonal antibodies directed against the β5 loop. The catalytic activity of the PL-antibody complexes on water insoluble substrates decreased drastically, whereas their esterase activity on a soluble substrate remained unchanged. During the last few years, a number of protein structures (15-lipoxygenase, a-toxin from Clostridium perfringens) have been determined that contain domains with close structural homologies with the β- sandwich C-terminal domain of PL. Generally speaking, these domains show structural homologies with the C2 domains occurring in a wide range of proteins involved in signal transduction (e.g. phosphoinositide-specific phospholipase C, protein kinase C, cytosolic phospholipase A2), membrane traffic (e.g. synaptotagmin I, rabphilin) and membrane disruption (e.g. perforin). Here it is proposed to review the structure and function of the C2 domains, based on the recent 3D structures and improved sequence alignments.
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H. Chahinian, B. Sias and F. Carriere, The C-Terminal Domain of Pancreatic Lipase: Functional and Structural Analogies with C2 Domains, Current Protein & Peptide Science 2000; 1 (1) . https://dx.doi.org/10.2174/1389203003381487
DOI https://dx.doi.org/10.2174/1389203003381487 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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