1lpb

THE 2.46 ANGSTROMS RESOLUTION STRUCTURE OF THE PANCREATIC LIPASE COLIPASE COMPLEX INHIBITED BY A C11 ALKYL PHOSPHONATETHE 2.46 ANGSTROMS RESOLUTION STRUCTURE OF THE PANCREATIC LIPASE COLIPASE COMPLEX INHIBITED BY A C11 ALKYL PHOSPHONATE

Structural highlights 1lpb is a 2 chain structure with sequence from Human and Pig. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , Activity: Triacylglycerol lipase, with EC number 3.1.1.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [COL_PIG] Colipase is a cofactor of pancreatic lipase. It allows the lipase to anchor itself to the lipid-water interface. Without colipase the enzyme is washed off by bile salts, which have an inhibitory effect on the lipase. Enterostatin has a biological activity as a satiety signal. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Pancreatic lipase belongs to the serine esterase family and can therefore be inhibited by classical serine reagents such as diisopropyl fluoride or E600. In an attempt to further characterize the active site and catalytic mechanism, we synthesized a C11 alkyl phosphonate compound. This compound is an effective inhibitor of pancreatic lipase. The crystal structure of the pancreatic lipase-colipase complex inhibited by this compound was determined at a resolution of 2.46 A and refined to a final R-factor of 18.3%. As was observed in the case of the structure of the ternary pancreatic lipase-colipase-phospholipid complex, the binding of the ligand induces rearrangements of two surface loops in comparison with the closed structure of the enzyme (van Tilbeurgh et al., 1993b). The inhibitor, which could be clearly observed in the active site, was covalently bound to the active site serine Ser152. A racemic mixture of the inhibitor was used in the crystallization, and there exists evidence that both enantiomers are bound at the active site. The C11 alkyl chain of the first enantiomer fits into a hydrophobic groove and is though to thus mimic the interaction between the leaving fatty acid of a triglyceride substrate and the protein. The alkyl chain of the second enantiomer also has an elongated conformation and interacts with hydrophobic patches on the surface of the open amphipathic lid. This may indicate the location of a second alkyl chain of a triglyceride substrate. Some of the detergent molecules, needed for the crystallization, were also observed in the crystal. Some of them were located at the entrance of the active site, bound to the hydrophobic part of the lid. On the basis of this crystallographic study, a hypothesis about the binding mode of real substrates and the organization of the active site is proposed. The 2.46 A resolution structure of the pancreatic lipase-colipase complex inhibited by a C11 alkyl phosphonate.,Egloff MP, Marguet F, Buono G, Verger R, Cambillau C, van Tilbeurgh H Biochemistry. 1995 Mar 7;34(9):2751-62. PMID:7893686 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Lipase 3D Structures

spinqualitylabelsall models 1lpb, resolution 2.46Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image