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1jmy

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[[Image:1jmy.jpg|left|200px]]<br /><applet load="1jmy" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1jmy, resolution 2.60&Aring;" />
 
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'''Truncated Recombinant Human Bile Salt Stimulated Lipase'''<br />
 
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==Overview==
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==Truncated Recombinant Human Bile Salt Stimulated Lipase==
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Human bile salt-stimulated lipase (BSSL), which is secreted from the pancreas into the digestive tract and from the lactating mammary gland into human milk, is important for the effective absorption of dietary lipids. The dependence of BSSL on bile acids for activity with water-insoluble substrates differentiates it from other lipases. We have determined the crystal structure of a truncated variant of human BSSL (residues 1-5.8) and refined it at 2.60 A resolution, to an R-factor of 0.238 and R(free) of 0.275. This variant lacks the C-terminal alpha-helix and tandem C-terminal repeat region of native BSSL, but retains full catalytic activity. A short loop (residues 115-126) capable of occluding the active-site (the active site loop) is highly mobile and exists in two conformations, the most predominant of which leaves the active-site open for interactions with substrate. The bile salt analogue 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonic acid (CHAPS) was present in the crystallisation medium, but was not observed bound to the enzyme. However, the structure reveals a sulfonate group from the buffer piperizine ethane sulfonic acid (PIPES), making interactions with Arg63 and His115. His115 is part of the active-site loop, indicating that the loop could participate in the binding of a sulphate group from either the glycosaminoglycan heparin (known to bind BSSL) or a bile acid such as deoxycholate. Opening of the 115-126 active-site loop may be cooperatively linked to a sulphate anion binding at this site. The helix bundle domain of BSSL (residues 319-398) exhibits weak electron density and high temperature factors, indicating considerable structural mobility. This domain contains an unusual Asp:Glu pair buried in a hydrophobic pocket between helices alpha(H) and alpha(K) that may be functionally important. We have also solved the structure of full-length glycosylated human BSSL at 4.1 A resolution, using the refined coordinates of the truncated molecule as a search model. This structure reveals the position of the C-terminal helix, missing in the truncated variant, and also shows the active-site loop to be in a closed conformation.
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<StructureSection load='1jmy' size='340' side='right'caption='[[1jmy]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1jmy]] 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=1JMY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JMY FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jmy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jmy OCA], [https://pdbe.org/1jmy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jmy RCSB], [https://www.ebi.ac.uk/pdbsum/1jmy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jmy ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jm/1jmy_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1jmy ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known disease associated with this structure: Maturity-onset diabetes of the young, type VIII OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=114840 114840]]
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*[[Cholesterol esterase 3D structures|Cholesterol esterase 3D structures]]
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*[[Lipase 3D Structures|Lipase 3D Structures]]
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==About this Structure==
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== References ==
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1JMY 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=SO4:'>SO4</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=1JMY OCA].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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The structure of truncated recombinant human bile salt-stimulated lipase reveals bile salt-independent conformational flexibility at the active-site loop and provides insights into heparin binding., Moore SA, Kingston RL, Loomes KM, Hernell O, Blackberg L, Baker HM, Baker EN, J Mol Biol. 2001 Sep 21;312(3):511-23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11563913 11563913]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Triacylglycerol lipase]]
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[[Category: Baker EN]]
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[[Category: Baker, E N.]]
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[[Category: Baker HM]]
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[[Category: Baker, H M.]]
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[[Category: Blackberg L]]
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[[Category: Blackberg, L.]]
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[[Category: Hernell O]]
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[[Category: Hernell, O.]]
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[[Category: Kingston RL]]
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[[Category: Kingston, R L.]]
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[[Category: Loomes KM]]
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[[Category: Loomes, K M.]]
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[[Category: Moore SA]]
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[[Category: Moore, S A.]]
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[[Category: SO4]]
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[[Category: bile salt dependent lipase]]
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[[Category: bile salt stimulated lipase]]
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[[Category: bsdl]]
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[[Category: bssl]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:24:25 2008''
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Current revision

Truncated Recombinant Human Bile Salt Stimulated Lipase

PDB ID 1jmy

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