1k8q
From Proteopedia
(New page: 200px<br /><applet load="1k8q" size="450" color="white" frame="true" align="right" spinBox="true" caption="1k8q, resolution 2.7Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1k8q.gif|left|200px]]<br /><applet load="1k8q" size=" | + | [[Image:1k8q.gif|left|200px]]<br /><applet load="1k8q" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1k8q, resolution 2.7Å" /> | caption="1k8q, resolution 2.7Å" /> | ||
'''CRYSTAL STRUCTURE OF DOG GASTRIC LIPASE IN COMPLEX WITH A PHOSPHONATE INHIBITOR'''<br /> | '''CRYSTAL STRUCTURE OF DOG GASTRIC LIPASE IN COMPLEX WITH A PHOSPHONATE INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Fat digestion in humans and some mammals such as dogs requires the | + | Fat digestion in humans and some mammals such as dogs requires the successive intervention of two lipases: gastric lipase, which is stable and active despite the highly acidic stomach environment, followed by the classical pancreatic lipase secreted into the duodenum. We previously solved the structure of recombinant human gastric lipase (HGL) at 3.0-A resolution in its closed form; this was the first structure to be described within the mammalian acid lipase family. Here we report on the open structure of the recombinant dog gastric lipase (r-DGL) at 2.7-A resolution in complex with the undecyl-butyl (C11Y4) phosphonate inhibitor. HGL and r-DGL show 85.7% amino acid sequence identity, which makes it relevant to compare the forms from two different species. The open r-DGL structure confirms the previous description of the HGL catalytic triad (Ser(153), His(353), and Asp(324)) with the catalytic serine buried and an oxyanion hole (NH groups of Gln(154) and Leu(67)). In r-DGL, the binding of the C11Y4 phosphonate inhibitor induces part of the cap domain, the lid, to roll over the enzyme surface and to expose a catalytic crevice measuring approximately 20 x 20 x 7 A(3). The C11Y4 phosphonate fits into this crevice, and a molecule of beta-octyl glucoside fills up the crevice. The C11Y4 phosphonate inhibitor and the detergent molecule suggest a possible binding mode for the natural substrates, the triglyceride molecules. |
==About this Structure== | ==About this Structure== | ||
| - | 1K8Q is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris] with NAG, BOG and C11 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:// | + | 1K8Q is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=BOG:'>BOG</scene> and <scene name='pdbligand=C11:'>C11</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=1K8Q OCA]. |
==Reference== | ==Reference== | ||
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[[Category: apha beta hydrolase fold]] | [[Category: apha beta hydrolase fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:31:20 2008'' |
Revision as of 11:31, 21 February 2008
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CRYSTAL STRUCTURE OF DOG GASTRIC LIPASE IN COMPLEX WITH A PHOSPHONATE INHIBITOR
Overview
Fat digestion in humans and some mammals such as dogs requires the successive intervention of two lipases: gastric lipase, which is stable and active despite the highly acidic stomach environment, followed by the classical pancreatic lipase secreted into the duodenum. We previously solved the structure of recombinant human gastric lipase (HGL) at 3.0-A resolution in its closed form; this was the first structure to be described within the mammalian acid lipase family. Here we report on the open structure of the recombinant dog gastric lipase (r-DGL) at 2.7-A resolution in complex with the undecyl-butyl (C11Y4) phosphonate inhibitor. HGL and r-DGL show 85.7% amino acid sequence identity, which makes it relevant to compare the forms from two different species. The open r-DGL structure confirms the previous description of the HGL catalytic triad (Ser(153), His(353), and Asp(324)) with the catalytic serine buried and an oxyanion hole (NH groups of Gln(154) and Leu(67)). In r-DGL, the binding of the C11Y4 phosphonate inhibitor induces part of the cap domain, the lid, to roll over the enzyme surface and to expose a catalytic crevice measuring approximately 20 x 20 x 7 A(3). The C11Y4 phosphonate fits into this crevice, and a molecule of beta-octyl glucoside fills up the crevice. The C11Y4 phosphonate inhibitor and the detergent molecule suggest a possible binding mode for the natural substrates, the triglyceride molecules.
About this Structure
1K8Q is a Single protein structure of sequence from Canis lupus familiaris with , and as ligands. Active as Triacylglycerol lipase, with EC number 3.1.1.3 Full crystallographic information is available from OCA.
Reference
Crystal structure of the open form of dog gastric lipase in complex with a phosphonate inhibitor., Roussel A, Miled N, Berti-Dupuis L, Riviere M, Spinelli S, Berna P, Gruber V, Verger R, Cambillau C, J Biol Chem. 2002 Jan 18;277(3):2266-74. Epub 2001 Oct 31. PMID:11689574
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