1lpb: Difference between revisions

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New page: left|200px<br /> <applet load="1lpb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lpb, resolution 2.46Å" /> '''THE 2.46 ANGSTROMS ...
 
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[[Image:1lpb.gif|left|200px]]<br />
<applet load="1lpb" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1lpb, resolution 2.46&Aring;" />
'''THE 2.46 ANGSTROMS RESOLUTION STRUCTURE OF THE PANCREATIC LIPASE COLIPASE COMPLEX INHIBITED BY A C11 ALKYL PHOSPHONATE'''<br />


==Overview==
==THE 2.46 ANGSTROMS RESOLUTION STRUCTURE OF THE PANCREATIC LIPASE COLIPASE COMPLEX INHIBITED BY A C11 ALKYL PHOSPHONATE==
Pancreatic lipase belongs to the serine esterase family and can therefore, be inhibited by classical serine reagents such as diisopropyl fluoride or, E600. In an attempt to further characterize the active site and catalytic, mechanism, we synthesized a C11 alkyl phosphonate compound. This compound, is an effective inhibitor of pancreatic lipase. The crystal structure of, the pancreatic lipase-colipase complex inhibited by this compound was, determined at a resolution of 2.46 A and refined to a final R-factor of, 18.3%. As was observed in the case of the structure of the ternary, pancreatic lipase-colipase-phospholipid complex, the binding of the ligand, induces rearrangements of two surface loops in comparison with the closed, structure of the enzyme (van Tilbeurgh et al., 1993b). The inhibitor, which could be clearly observed in the active site, was covalently bound, to the active site serine Ser152. A racemic mixture of the inhibitor was, used in the crystallization, and there exists evidence that both, enantiomers are bound at the active site. The C11 alkyl chain of the first, enantiomer fits into a hydrophobic groove and is though to thus mimic the, interaction between the leaving fatty acid of a triglyceride substrate and, the protein. The alkyl chain of the second enantiomer also has an, elongated conformation and interacts with hydrophobic patches on the, surface of the open amphipathic lid. This may indicate the location of a, second alkyl chain of a triglyceride substrate. Some of the detergent, molecules, needed for the crystallization, were also observed in the, crystal. Some of them were located at the entrance of the active site, bound to the hydrophobic part of the lid. On the basis of this, crystallographic study, a hypothesis about the binding mode of real, substrates and the organization of the active site is proposed.
<StructureSection load='1lpb' size='340' side='right'caption='[[1lpb]], [[Resolution|resolution]] 2.46&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1lpb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LPB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.46&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MUP:METHOXYUNDECYLPHOSPHINIC+ACID'>MUP</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=1lpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lpb OCA], [https://pdbe.org/1lpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lpb RCSB], [https://www.ebi.ac.uk/pdbsum/1lpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lpb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/COL_PIG COL_PIG] Colipase is a cofactor of pancreatic lipase. It allows the lipase to anchor itself to the lipid-water interface. Without colipase the enzyme is washed off by bile salts, which have an inhibitory effect on the lipase. Enterostatin has a biological activity as a satiety signal.
== 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/lp/1lpb_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1lpb ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known disease associated with this structure: Pancreatic lipase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=246600 246600]]
*[[Lipase 3D Structures|Lipase 3D Structures]]
 
__TOC__
==About this Structure==
</StructureSection>
1LPB is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with BOG, CA and MUP 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LPB OCA].
 
==Reference==
The 2.46 A resolution structure of the pancreatic lipase-colipase complex inhibited by a C11 alkyl phosphonate., Egloff MP, Marguet F, Buono G, Verger R, Cambillau C, van Tilbeurgh H, Biochemistry. 1995 Mar 7;34(9):2751-62. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7893686 7893686]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Sus scrofa]]
[[Category: Triacylglycerol lipase]]
[[Category: Cambillau C]]
[[Category: Cambillau, C.]]
[[Category: Egloff M-P]]
[[Category: Egloff, M.P.]]
[[Category: Van Tilbeurgh H]]
[[Category: Tilbeurgh, H.Van.]]
[[Category: BOG]]
[[Category: CA]]
[[Category: MUP]]
[[Category: hydrolase(carboxylic esterase)]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:03:06 2007''

Latest revision as of 11:25, 10 April 2024

THE 2.46 ANGSTROMS RESOLUTION STRUCTURE OF THE PANCREATIC LIPASE COLIPASE COMPLEX INHIBITED BY A C11 ALKYL PHOSPHONATETHE 2.46 ANGSTROMS RESOLUTION STRUCTURE OF THE PANCREATIC LIPASE COLIPASE COMPLEX INHIBITED BY A C11 ALKYL PHOSPHONATE

Structural highlights

1lpb is a 2 chain structure with sequence from Homo sapiens and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.46Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

COL_PIG Colipase is a cofactor of pancreatic lipase. It allows the lipase to anchor itself to the lipid-water interface. Without colipase the enzyme is washed off by bile salts, which have an inhibitory effect on the lipase. Enterostatin has a biological activity as a satiety signal.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1lpb, resolution 2.46Å

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