1hlg
From Proteopedia
(New page: 200px<br /> <applet load="1hlg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hlg, resolution 3.Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1hlg.gif|left|200px]]<br /> | + | [[Image:1hlg.gif|left|200px]]<br /><applet load="1hlg" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1hlg" size=" | + | |
caption="1hlg, resolution 3.Å" /> | caption="1hlg, resolution 3.Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN GASTRIC LIPASE'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN GASTRIC LIPASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Fat digestion in humans requires not only the classical pancreatic lipase | + | Fat digestion in humans requires not only the classical pancreatic lipase but also gastric lipase, which is stable and active despite the highly acidic stomach environment. We report here the structure of recombinant human gastric lipase at 3.0-A resolution, the first structure to be described within the mammalian acid lipase family. This globular enzyme (379 residues) consists of a core domain belonging to the alpha/beta hydrolase-fold family and a "cap" domain, which is analogous to that present in serine carboxypeptidases. It possesses a classical catalytic triad (Ser-153, His-353, Asp-324) and an oxyanion hole (NH groups of Gln-154 and Leu-67). Four N-glycosylation sites were identified on the electron density maps. The catalytic serine is deeply buried under a segment consisting of 30 residues, which can be defined as a lid and belonging to the cap domain. The displacement of the lid is necessary for the substrates to have access to Ser-153. A phosphonate inhibitor was positioned in the active site that clearly suggests the location of the hydrophobic substrate binding site. The lysosomal acid lipase was modeled by homology, and possible explanations for some previously reported mutations leading to the cholesterol ester storage disease are given based on the present model. |
==About this Structure== | ==About this Structure== | ||
| - | 1HLG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 1HLG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1HLG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: lipase]] | [[Category: lipase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:02:29 2008'' |
Revision as of 11:02, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN GASTRIC LIPASE
Overview
Fat digestion in humans requires not only the classical pancreatic lipase but also gastric lipase, which is stable and active despite the highly acidic stomach environment. We report here the structure of recombinant human gastric lipase at 3.0-A resolution, the first structure to be described within the mammalian acid lipase family. This globular enzyme (379 residues) consists of a core domain belonging to the alpha/beta hydrolase-fold family and a "cap" domain, which is analogous to that present in serine carboxypeptidases. It possesses a classical catalytic triad (Ser-153, His-353, Asp-324) and an oxyanion hole (NH groups of Gln-154 and Leu-67). Four N-glycosylation sites were identified on the electron density maps. The catalytic serine is deeply buried under a segment consisting of 30 residues, which can be defined as a lid and belonging to the cap domain. The displacement of the lid is necessary for the substrates to have access to Ser-153. A phosphonate inhibitor was positioned in the active site that clearly suggests the location of the hydrophobic substrate binding site. The lysosomal acid lipase was modeled by homology, and possible explanations for some previously reported mutations leading to the cholesterol ester storage disease are given based on the present model.
About this Structure
1HLG is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Triacylglycerol lipase, with EC number 3.1.1.3 Full crystallographic information is available from OCA.
Reference
Crystal structure of human gastric lipase and model of lysosomal acid lipase, two lipolytic enzymes of medical interest., Roussel A, Canaan S, Egloff MP, Riviere M, Dupuis L, Verger R, Cambillau C, J Biol Chem. 1999 Jun 11;274(24):16995-7002. PMID:10358049
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