1dt5
From Proteopedia
(New page: 200px<br /><applet load="1dt5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dt5, resolution 2.4Å" /> '''THE STRUCTURAL ORIGIN...) |
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| - | [[Image:1dt5.gif|left|200px]]<br /><applet load="1dt5" size=" | + | [[Image:1dt5.gif|left|200px]]<br /><applet load="1dt5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1dt5, resolution 2.4Å" /> | caption="1dt5, resolution 2.4Å" /> | ||
'''THE STRUCTURAL ORIGINS OF INTERFACIAL ACTIVATION IN THERMOMYCES (HUMICOLA) LANUGINOSA LIPASE'''<br /> | '''THE STRUCTURAL ORIGINS OF INTERFACIAL ACTIVATION IN THERMOMYCES (HUMICOLA) LANUGINOSA LIPASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The already known X-ray structures of lipases provide little evidence | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1DT5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermomyces_lanuginosus Thermomyces lanuginosus]. 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:// | + | 1DT5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermomyces_lanuginosus Thermomyces lanuginosus]. 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=1DT5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Thermomyces lanuginosus]] | [[Category: Thermomyces lanuginosus]] | ||
[[Category: Triacylglycerol lipase]] | [[Category: Triacylglycerol lipase]] | ||
| - | [[Category: Brozozowski, A | + | [[Category: Brozozowski, A M.]] |
[[Category: Savage, H.]] | [[Category: Savage, H.]] | ||
[[Category: alpha-beta protein]] | [[Category: alpha-beta protein]] | ||
| Line 21: | Line 21: | ||
[[Category: thermomyces linuginosa]] | [[Category: thermomyces linuginosa]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:20:11 2008'' |
Revision as of 10:20, 21 February 2008
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THE STRUCTURAL ORIGINS OF INTERFACIAL ACTIVATION IN THERMOMYCES (HUMICOLA) LANUGINOSA LIPASE
Overview
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.
About this Structure
1DT5 is a Single protein structure of sequence from Thermomyces lanuginosus. Active as Triacylglycerol lipase, with EC number 3.1.1.3 Full crystallographic information is available from OCA.
Reference
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
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