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| - | [[Image:1hlg.gif|left|200px]] | |
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| - | {{Structure
| + | ==CRYSTAL STRUCTURE OF HUMAN GASTRIC LIPASE== |
| - | |PDB= 1hlg |SIZE=350|CAPTION= <scene name='initialview01'>1hlg</scene>, resolution 3.Å
| + | <StructureSection load='1hlg' size='340' side='right'caption='[[1hlg]], [[Resolution|resolution]] 3.00Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> | + | <table><tr><td colspan='2'>[[1hlg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HLG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HLG FirstGlance]. <br> |
| - | |ACTIVITY= [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]
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| - | |GENE= | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hlg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hlg OCA], [https://pdbe.org/1hlg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hlg RCSB], [https://www.ebi.ac.uk/pdbsum/1hlg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hlg ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/LIPF_HUMAN LIPF_HUMAN] Catalyzes the hydrolysis of triacylglycerols to yield free fatty acids, diacylglycerol, monoacylglycerol, and glycerol (PubMed:10358049, PubMed:2243091). Shows a preferential hydrolysis at the sn-3 position of triacylglycerol (PubMed:2243091).<ref>PMID:10358049</ref> <ref>PMID:2243091</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hl/1hlg_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hlg ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | 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. |
| | | | |
| - | '''CRYSTAL STRUCTURE OF HUMAN GASTRIC LIPASE'''
| + | 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<ref>PMID:10358049</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 1hlg" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Overview== | + | ==See Also== |
| - | 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.
| + | *[[Lipase 3D Structures|Lipase 3D Structures]] |
| - | | + | == References == |
| - | ==About this Structure==
| + | <references/> |
| - | 1HLG is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HLG OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==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:[http://www.ncbi.nlm.nih.gov/pubmed/10358049 10358049]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Triacylglycerol lipase]]
| + | [[Category: Cambillau C]] |
| - | [[Category: Cambillau, C.]] | + | [[Category: Canaan S]] |
| - | [[Category: Canaan, S.]] | + | [[Category: Roussel A]] |
| - | [[Category: Roussel, A.]] | + | [[Category: Verger R]] |
| - | [[Category: Verger, R.]] | + | |
| - | [[Category: NAG]]
| + | |
| - | [[Category: lipase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:38:37 2008''
| + | |
| Structural highlights
Function
LIPF_HUMAN Catalyzes the hydrolysis of triacylglycerols to yield free fatty acids, diacylglycerol, monoacylglycerol, and glycerol (PubMed:10358049, PubMed:2243091). Shows a preferential hydrolysis at the sn-3 position of triacylglycerol (PubMed:2243091).[1] [2]
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
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.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Roussel A, Canaan S, Egloff MP, Riviere M, Dupuis L, Verger R, Cambillau C. Crystal structure of human gastric lipase and model of lysosomal acid lipase, two lipolytic enzymes of medical interest. J Biol Chem. 1999 Jun 11;274(24):16995-7002. PMID:10358049
- ↑ Rogalska E, Ransac S, Verger R. Stereoselectivity of lipases. II. Stereoselective hydrolysis of triglycerides by gastric and pancreatic lipases. J Biol Chem. 1990 Nov 25;265(33):20271-6 PMID:2243091
- ↑ Roussel A, Canaan S, Egloff MP, Riviere M, Dupuis L, Verger R, Cambillau C. Crystal structure of human gastric lipase and model of lysosomal acid lipase, two lipolytic enzymes of medical interest. J Biol Chem. 1999 Jun 11;274(24):16995-7002. PMID:10358049
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