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| | <StructureSection load='6h0t' size='340' side='right'caption='[[6h0t]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='6h0t' size='340' side='right'caption='[[6h0t]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6h0t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H0T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H0T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6h0t]] is a 1 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=6H0T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6H0T FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6h0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h0t OCA], [http://pdbe.org/6h0t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h0t RCSB], [http://www.ebi.ac.uk/pdbsum/6h0t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h0t ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6h0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h0t OCA], [https://pdbe.org/6h0t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6h0t RCSB], [https://www.ebi.ac.uk/pdbsum/6h0t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6h0t ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CEL_HUMAN CEL_HUMAN]] Defects in CEL are a cause of maturity-onset diabetes of the young type 8 with exocrine dysfunction (MODY8) [MIM:[http://omim.org/entry/609812 609812]]; also known as diabetes and pancreatic exocrine dysfunction (DPED). MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:16369531</ref> | + | [https://www.uniprot.org/uniprot/CEL_HUMAN CEL_HUMAN] Defects in CEL are a cause of maturity-onset diabetes of the young type 8 with exocrine dysfunction (MODY8) [MIM:[https://omim.org/entry/609812 609812]; also known as diabetes and pancreatic exocrine dysfunction (DPED). MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:16369531</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CEL_HUMAN CEL_HUMAN]] Catalyzes fat and vitamin absorption. Acts in concert with pancreatic lipase and colipase for the complete digestion of dietary triglycerides. | + | [https://www.uniprot.org/uniprot/CEL_HUMAN CEL_HUMAN] Catalyzes fat and vitamin absorption. Acts in concert with pancreatic lipase and colipase for the complete digestion of dietary triglycerides. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6h0t" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6h0t" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cholesterol esterase 3D structures|Cholesterol esterase 3D structures]] |
| | + | *[[Lipase 3D Structures|Lipase 3D Structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Brazzolotto, X]] | + | [[Category: Brazzolotto X]] |
| - | [[Category: Nachon, F]] | + | [[Category: Nachon F]] |
| - | [[Category: Touvrey, C]] | + | [[Category: Touvrey C]] |
| - | [[Category: Alpha-beta hydrolase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lipase]]
| + | |
| Structural highlights
Disease
CEL_HUMAN Defects in CEL are a cause of maturity-onset diabetes of the young type 8 with exocrine dysfunction (MODY8) [MIM:609812; also known as diabetes and pancreatic exocrine dysfunction (DPED). MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.[1]
Function
CEL_HUMAN Catalyzes fat and vitamin absorption. Acts in concert with pancreatic lipase and colipase for the complete digestion of dietary triglycerides.
Publication Abstract from PubMed
The efficiency of human butyrylcholinesterase (BChE) as a stoichiometric bioscavenger of nerve agents is well established. However, wide use is currently limited by production and purification costs. Aiming at identifying an alternative human protein bioscavenger, we looked for an original scaffold candidate by virtual screening of the Protein Data Bank for functional similarity using the "Surfing the Molecules" software (sumo-pbil.ibcp.fr) and a search model based on the BChE active site topology. Besides the expected acetylcholinesterase and butyrylcholinesterase, we identified a set of bile salt activated lipases structures, among which the human pancreatic lipase (hBAL) that shares 34% identity with BChE. We produced the recombinant enzyme in mammalian cells, purified it, and measured the inhibition constants for paraoxon and surrogates of VX, sarin and tabun. We solved the X-ray structure of apo hBAL and conjugates with paraoxon and the surrogates at resolutions in the 2-A range. These structures allow the assessment of hBAL for scavenging nerve agents. They revealed that hBAL has inverted stereoselectivity for the surrogates of nerve agent compared to human cholinesterases. We observed a remarkable flip of the catalytic histidine driven by the chelation of Zn(2+). Dealkylation of the conjugate, aka aging, was solely observed for paraoxon.
X-ray structures of human bile-salt activated lipase conjugated to nerve agents surrogates.,Touvrey C, Courageux C, Guillon V, Terreux R, Nachon F, Brazzolotto X Toxicology. 2019 Jan 1;411:15-23. doi: 10.1016/j.tox.2018.10.015. Epub 2018 Oct, 22. PMID:30359675[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Raeder H, Johansson S, Holm PI, Haldorsen IS, Mas E, Sbarra V, Nermoen I, Eide SA, Grevle L, Bjorkhaug L, Sagen JV, Aksnes L, Sovik O, Lombardo D, Molven A, Njolstad PR. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction. Nat Genet. 2006 Jan;38(1):54-62. Epub 2005 Dec 20. PMID:16369531 doi:10.1038/ng1708
- ↑ Touvrey C, Courageux C, Guillon V, Terreux R, Nachon F, Brazzolotto X. X-ray structures of human bile-salt activated lipase conjugated to nerve agents surrogates. Toxicology. 2019 Jan 1;411:15-23. doi: 10.1016/j.tox.2018.10.015. Epub 2018 Oct, 22. PMID:30359675 doi:http://dx.doi.org/10.1016/j.tox.2018.10.015
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