1sng
From Proteopedia
(New page: 200px<br /><applet load="1sng" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sng, resolution 1.76Å" /> '''Structure of a Therm...) |
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| - | [[Image:1sng.gif|left|200px]]<br /><applet load="1sng" size=" | + | [[Image:1sng.gif|left|200px]]<br /><applet load="1sng" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1sng, resolution 1.76Å" /> | caption="1sng, resolution 1.76Å" /> | ||
'''Structure of a Thermophilic Serpin in the Native State'''<br /> | '''Structure of a Thermophilic Serpin in the Native State'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Serpins fold into a native metastable state and utilize a complex | + | Serpins fold into a native metastable state and utilize a complex conformational change to inhibit target proteases. An undesirable result of this conformational flexibility is that most inhibitory serpins are heat sensitive, forming inactive polymers at elevated temperatures. However, the prokaryote serpin, thermopin, from Thermobifida fusca is able to function in a heated environment. We have determined the 1.8 A x-ray crystal structure of thermopin in the native, inhibitory conformation. A structural comparison with the previously determined 1.5 A structure of cleaved thermopin provides detailed insight into the complex mechanism of conformational change in serpins. Flexibility in the shutter region and electrostatic interactions at the top of the A beta-sheet (the breach) involving the C-terminal tail, a unique structural feature of thermopin, are postulated to be important for controlling inhibitory activity and triggering conformational change, respectively, in the native state. Here we have discussed the structural basis of how this serpin reconciles the thermodynamic instability necessary for function with the stability required to withstand elevated temperatures. |
==About this Structure== | ==About this Structure== | ||
| - | 1SNG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermobifida_fusca Thermobifida fusca] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1SNG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermobifida_fusca Thermobifida fusca] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SNG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thermobifida fusca]] | [[Category: Thermobifida fusca]] | ||
| - | [[Category: Bottomley, S | + | [[Category: Bottomley, S P.]] |
| - | [[Category: Buckle, A | + | [[Category: Buckle, A M.]] |
| - | [[Category: Butcher, R | + | [[Category: Butcher, R E.]] |
| - | [[Category: Cabrita, L | + | [[Category: Cabrita, L D.]] |
| - | [[Category: Fulton, K | + | [[Category: Fulton, K F.]] |
| - | [[Category: Irving, J | + | [[Category: Irving, J A.]] |
| - | [[Category: Lesk, A | + | [[Category: Lesk, A M.]] |
[[Category: Reeve, S.]] | [[Category: Reeve, S.]] | ||
[[Category: Rossjohn, J.]] | [[Category: Rossjohn, J.]] | ||
[[Category: Smith, I.]] | [[Category: Smith, I.]] | ||
| - | [[Category: Whisstock, J | + | [[Category: Whisstock, J C.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: native state.]] | [[Category: native state.]] | ||
[[Category: serine protease inhibitor (serpin)]] | [[Category: serine protease inhibitor (serpin)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:03:20 2008'' |
Revision as of 13:03, 21 February 2008
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Structure of a Thermophilic Serpin in the Native State
Overview
Serpins fold into a native metastable state and utilize a complex conformational change to inhibit target proteases. An undesirable result of this conformational flexibility is that most inhibitory serpins are heat sensitive, forming inactive polymers at elevated temperatures. However, the prokaryote serpin, thermopin, from Thermobifida fusca is able to function in a heated environment. We have determined the 1.8 A x-ray crystal structure of thermopin in the native, inhibitory conformation. A structural comparison with the previously determined 1.5 A structure of cleaved thermopin provides detailed insight into the complex mechanism of conformational change in serpins. Flexibility in the shutter region and electrostatic interactions at the top of the A beta-sheet (the breach) involving the C-terminal tail, a unique structural feature of thermopin, are postulated to be important for controlling inhibitory activity and triggering conformational change, respectively, in the native state. Here we have discussed the structural basis of how this serpin reconciles the thermodynamic instability necessary for function with the stability required to withstand elevated temperatures.
About this Structure
1SNG is a Single protein structure of sequence from Thermobifida fusca with as ligand. Full crystallographic information is available from OCA.
Reference
The high resolution crystal structure of a native thermostable serpin reveals the complex mechanism underpinning the stressed to relaxed transition., Fulton KF, Buckle AM, Cabrita LD, Irving JA, Butcher RE, Smith I, Reeve S, Lesk AM, Bottomley SP, Rossjohn J, Whisstock JC, J Biol Chem. 2005 Mar 4;280(9):8435-42. Epub 2004 Dec 7. PMID:15590653
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