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==THE STRUCTURAL ORIGINS OF INTERFACIAL ACTIVATION IN THERMOMYCES (HUMICOLA) LANUGINOSA LIPASE OTHER STRUCTURE DETAILS== | |||
<StructureSection load='1du4' size='340' side='right'caption='[[1du4]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1du4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermomyces_lanuginosus Thermomyces lanuginosus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DU4 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]] 2.5Å</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=1du4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1du4 OCA], [https://pdbe.org/1du4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1du4 RCSB], [https://www.ebi.ac.uk/pdbsum/1du4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1du4 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LIP_THELA LIP_THELA] | |||
== 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/du/1du4_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=1du4 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The already known X-ray structures of lipases provide little evidence about initial, discrete structural steps occurring in the first phases of their activation in the presence of lipids (process referred to as interfacial activation). To address this problem, five new Thermomyces (formerly Humicola) lanuginosa lipase (TlL) crystal structures have been solved and compared with four previously reported structures of this enzyme. The bias coming from different crystallization media has been minimized by the growth of all crystals under the same crystallization conditions, in the presence of detergent/lipid analogues, with low or high ionic strength as the only main variable. Resulting structures and their characteristic features allowed the identification of three structurally distinct species of this enzyme: low activity form (LA), activated form (A), and fully Active (FA) form. The isomerization of the Cys268-Cys22 disulfide, synchronized with the formation of a new, short alpha(0) helix and flipping of the Arg84 (Arginine switch) located in the lid's proximal hinge, have been postulated as the key, structural factors of the initial transitions between LA and A forms. The experimental results were supplemented by theoretical calculations. The magnitude of the activation barrier between LA (ground state) and A (end state) forms of TlL (10.6 kcal/mol) is comparable to the enthalpic barriers typical for ring flips and disulfide isomerizations at ambient temperatures. This suggests that the sequence of the structural changes, as exemplified in various TlL crystal structures, mirror those that may occur during interfacial activation. | |||
Structural origins of the interfacial activation in Thermomyces (Humicola) lanuginosa lipase.,Brzozowski AM, Savage H, Verma CS, Turkenburg JP, Lawson DM, Svendsen A, Patkar S Biochemistry. 2000 Dec 12;39(49):15071-82. PMID:11106485<ref>PMID:11106485</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1du4" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Lipase|Lipase]] | *[[Lipase 3D Structures|Lipase 3D Structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Thermomyces lanuginosus]] | [[Category: Thermomyces lanuginosus]] | ||
[[Category: Brozozowski AM]] | |||
[[Category: Brozozowski | [[Category: Savage H]] | ||
[[Category: Savage | |||
Latest revision as of 07:27, 17 October 2024
THE STRUCTURAL ORIGINS OF INTERFACIAL ACTIVATION IN THERMOMYCES (HUMICOLA) LANUGINOSA LIPASE OTHER STRUCTURE DETAILSTHE STRUCTURAL ORIGINS OF INTERFACIAL ACTIVATION IN THERMOMYCES (HUMICOLA) LANUGINOSA LIPASE OTHER STRUCTURE DETAILS
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe already known X-ray structures of lipases provide little evidence about initial, discrete structural steps occurring in the first phases of their activation in the presence of lipids (process referred to as interfacial activation). To address this problem, five new Thermomyces (formerly Humicola) lanuginosa lipase (TlL) crystal structures have been solved and compared with four previously reported structures of this enzyme. The bias coming from different crystallization media has been minimized by the growth of all crystals under the same crystallization conditions, in the presence of detergent/lipid analogues, with low or high ionic strength as the only main variable. Resulting structures and their characteristic features allowed the identification of three structurally distinct species of this enzyme: low activity form (LA), activated form (A), and fully Active (FA) form. The isomerization of the Cys268-Cys22 disulfide, synchronized with the formation of a new, short alpha(0) helix and flipping of the Arg84 (Arginine switch) located in the lid's proximal hinge, have been postulated as the key, structural factors of the initial transitions between LA and A forms. The experimental results were supplemented by theoretical calculations. The magnitude of the activation barrier between LA (ground state) and A (end state) forms of TlL (10.6 kcal/mol) is comparable to the enthalpic barriers typical for ring flips and disulfide isomerizations at ambient temperatures. This suggests that the sequence of the structural changes, as exemplified in various TlL crystal structures, mirror those that may occur during interfacial activation. Structural origins of the interfacial activation in Thermomyces (Humicola) lanuginosa lipase.,Brzozowski AM, Savage H, Verma CS, Turkenburg JP, Lawson DM, Svendsen A, Patkar S Biochemistry. 2000 Dec 12;39(49):15071-82. PMID:11106485[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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