1eth
From Proteopedia
(New page: 200px<br /><applet load="1eth" size="450" color="white" frame="true" align="right" spinBox="true" caption="1eth, resolution 2.8Å" /> '''TRIACYLGLYCEROL LIPAS...) |
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| - | [[Image:1eth.gif|left|200px]]<br /><applet load="1eth" size=" | + | [[Image:1eth.gif|left|200px]]<br /><applet load="1eth" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1eth, resolution 2.8Å" /> | caption="1eth, resolution 2.8Å" /> | ||
'''TRIACYLGLYCEROL LIPASE/COLIPASE COMPLEX'''<br /> | '''TRIACYLGLYCEROL LIPASE/COLIPASE COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of the ternary porcine lipase-colipase-tetra | + | The crystal structure of the ternary porcine lipase-colipase-tetra ethylene glycol monooctyl ether (TGME) complex has been determined at 2.8 A resolution. The crystals belong to the cubic space group F23 with a = 289.1 A and display a strong pseudo-symmetry corresponding to a P23 lattice. Unexpectedly, the crystalline two-domain lipase is found in its open configuration. This indicates that in the presence of colipase, pure micelles of the nonionic detergent TGME are able to activate the enzyme; a process that includes the movement of an N-terminal domain loop (the flap). The effects of TGME and colipase have been confirmed by chemical modification of the active site serine residue using diisopropyl p-nitrophenylphosphate (E600). In addition, the presence of a TGME molecule tightly bound to the active site pocket shows that TGME acts as a substrate analog, thus possibly explaining the inhibitory effect of this nonionic detergent on emulsified substrate hydrolysis at submicellar concentrations. A comparison of the lipase-colipase interactions between our porcine complex and the human-porcine complex (van Tilbeurgh, H., Egloff, M.-P., Martinez, C., Rugani, N., Verger, R., and Cambillau, C.(1993) Nature 362, 814-820) indicates that except for one salt bridge interaction, they are conserved. Analysis of the superimposed complexes shows a 5.4 degrees rotation on the relative position of the N-terminal domains excepting the flap that moves in a concerted fashion with the C-terminal domain. This flexibility may be important for the binding of the complex to the water-lipid interface. |
==About this Structure== | ==About this Structure== | ||
| - | 1ETH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with CA, C8E and BME as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Triacylglycerol_lipase Triacylglycerol lipase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.3 3.1.1.3] Full crystallographic information is available from [http:// | + | 1ETH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=C8E:'>C8E</scene> and <scene name='pdbligand=BME:'>BME</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Triacylglycerol_lipase Triacylglycerol lipase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.3 3.1.1.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ETH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Chapus, C.]] | [[Category: Chapus, C.]] | ||
[[Category: Crenon, I.]] | [[Category: Crenon, I.]] | ||
| - | [[Category: Fontecilla-Camps, J | + | [[Category: Fontecilla-Camps, J C.]] |
[[Category: Hermoso, J.]] | [[Category: Hermoso, J.]] | ||
[[Category: Kerfelec, B.]] | [[Category: Kerfelec, B.]] | ||
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[[Category: lipid degradation]] | [[Category: lipid degradation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:31:19 2008'' |
Revision as of 10:31, 21 February 2008
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TRIACYLGLYCEROL LIPASE/COLIPASE COMPLEX
Overview
The crystal structure of the ternary porcine lipase-colipase-tetra ethylene glycol monooctyl ether (TGME) complex has been determined at 2.8 A resolution. The crystals belong to the cubic space group F23 with a = 289.1 A and display a strong pseudo-symmetry corresponding to a P23 lattice. Unexpectedly, the crystalline two-domain lipase is found in its open configuration. This indicates that in the presence of colipase, pure micelles of the nonionic detergent TGME are able to activate the enzyme; a process that includes the movement of an N-terminal domain loop (the flap). The effects of TGME and colipase have been confirmed by chemical modification of the active site serine residue using diisopropyl p-nitrophenylphosphate (E600). In addition, the presence of a TGME molecule tightly bound to the active site pocket shows that TGME acts as a substrate analog, thus possibly explaining the inhibitory effect of this nonionic detergent on emulsified substrate hydrolysis at submicellar concentrations. A comparison of the lipase-colipase interactions between our porcine complex and the human-porcine complex (van Tilbeurgh, H., Egloff, M.-P., Martinez, C., Rugani, N., Verger, R., and Cambillau, C.(1993) Nature 362, 814-820) indicates that except for one salt bridge interaction, they are conserved. Analysis of the superimposed complexes shows a 5.4 degrees rotation on the relative position of the N-terminal domains excepting the flap that moves in a concerted fashion with the C-terminal domain. This flexibility may be important for the binding of the complex to the water-lipid interface.
About this Structure
1ETH is a Protein complex structure of sequences from Sus scrofa with , and as ligands. Active as Triacylglycerol lipase, with EC number 3.1.1.3 Full crystallographic information is available from OCA.
Reference
Lipase activation by nonionic detergents. The crystal structure of the porcine lipase-colipase-tetraethylene glycol monooctyl ether complex., Hermoso J, Pignol D, Kerfelec B, Crenon I, Chapus C, Fontecilla-Camps JC, J Biol Chem. 1996 Jul 26;271(30):18007-16. PMID:8663362
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