2nw6: Difference between revisions
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== | ==Burkholderia cepacia lipase complexed with S-inhibitor== | ||
<StructureSection load='2nw6' size='340' side='right'caption='[[2nw6]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2nw6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_cepacia Burkholderia cepacia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NW6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NW6 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]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=POT:(1S)-1-(PHENOXYMETHYL)PROPYL+METHYLPHOSPHONOCHLORIDOATE'>POT</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=2nw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nw6 OCA], [https://pdbe.org/2nw6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nw6 RCSB], [https://www.ebi.ac.uk/pdbsum/2nw6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nw6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LIP_BURCE LIP_BURCE] Catalyzes the hydrolysis of triglycerides. | |||
== 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/nw/2nw6_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=2nw6 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
To understand the origin of high enantioselectivity of Burkholderia cepacia lipase (BCL) toward secondary alcohol, (R,S)-1-phenoxy-2-hydroxybutane (1), and its ester (E1), we determined the crystal structure of BCL complexed with phosphonate analogue of S-E1 and accomplished a series of MM, MC, and QM/MM studies. We have found that the inhibitor in the S configuration binds into the BCL active site in the same manner as the R isomer, with an important difference: while in case of the R-inhibitor the H-bond between its alcohol oxygen and catalytic His286 can be formed, in the case of the S-inhibitor this is not possible. Molecular modeling for both E1 enantiomers revealed orientations in which all hydrogen bonds characteristic of productive binding are formed. To check the possibility of chemical transformation, four different orientations of the substrate (two for each enantiomer) were chosen, and a series of ab initio QM/MM calculations were accomplished. Starting from the covalent complex, we modeled the ester (E1) hydrolysis and the alcohol (1) esterification. The calculations revealed that ester release is possible starting with all four covalent complexes. Alcohol release from the BCL-E1 complex in which the S-substrate is bound in the same manner as the S-inhibitor in the crystal structure however is not possible. These results show that the crystallographically determined binding modes should be taken with caution when modeling chemical reactions. | |||
Combined X-ray diffraction and QM/MM study of the Burkholderia cepacia lipase-catalyzed secondary alcohol esterification.,Luic M, Stefanic Z, Ceilinger I, Hodoscek M, Janezic D, Lenac T, Asler IL, Sepac D, Tomic S J Phys Chem B. 2008 Apr 24;112(16):4876-83. Epub 2008 Apr 3. PMID:18386861<ref>PMID:18386861</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2nw6" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Lipase 3D Structures|Lipase 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Burkholderia cepacia]] | [[Category: Burkholderia cepacia]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Luic M]] | |||
[[Category: Luic | [[Category: Stefanic Z]] | ||
[[Category: Stefanic | |||
Latest revision as of 10:43, 9 October 2024
Burkholderia cepacia lipase complexed with S-inhibitorBurkholderia cepacia lipase complexed with S-inhibitor
Structural highlights
FunctionLIP_BURCE Catalyzes the hydrolysis of triglycerides. 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 PubMedTo understand the origin of high enantioselectivity of Burkholderia cepacia lipase (BCL) toward secondary alcohol, (R,S)-1-phenoxy-2-hydroxybutane (1), and its ester (E1), we determined the crystal structure of BCL complexed with phosphonate analogue of S-E1 and accomplished a series of MM, MC, and QM/MM studies. We have found that the inhibitor in the S configuration binds into the BCL active site in the same manner as the R isomer, with an important difference: while in case of the R-inhibitor the H-bond between its alcohol oxygen and catalytic His286 can be formed, in the case of the S-inhibitor this is not possible. Molecular modeling for both E1 enantiomers revealed orientations in which all hydrogen bonds characteristic of productive binding are formed. To check the possibility of chemical transformation, four different orientations of the substrate (two for each enantiomer) were chosen, and a series of ab initio QM/MM calculations were accomplished. Starting from the covalent complex, we modeled the ester (E1) hydrolysis and the alcohol (1) esterification. The calculations revealed that ester release is possible starting with all four covalent complexes. Alcohol release from the BCL-E1 complex in which the S-substrate is bound in the same manner as the S-inhibitor in the crystal structure however is not possible. These results show that the crystallographically determined binding modes should be taken with caution when modeling chemical reactions. Combined X-ray diffraction and QM/MM study of the Burkholderia cepacia lipase-catalyzed secondary alcohol esterification.,Luic M, Stefanic Z, Ceilinger I, Hodoscek M, Janezic D, Lenac T, Asler IL, Sepac D, Tomic S J Phys Chem B. 2008 Apr 24;112(16):4876-83. Epub 2008 Apr 3. PMID:18386861[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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