4pro
From Proteopedia
(New page: 200px<br /><applet load="4pro" size="450" color="white" frame="true" align="right" spinBox="true" caption="4pro, resolution 2.4Å" /> '''ALPHA-LYTIC PROTEASE ...) |
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| - | [[Image:4pro.gif|left|200px]]<br /><applet load="4pro" size=" | + | [[Image:4pro.gif|left|200px]]<br /><applet load="4pro" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="4pro, resolution 2.4Å" /> | caption="4pro, resolution 2.4Å" /> | ||
'''ALPHA-LYTIC PROTEASE COMPLEXED WITH PRO REGION'''<br /> | '''ALPHA-LYTIC PROTEASE COMPLEXED WITH PRO REGION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | While the majority of proteins fold rapidly and spontaneously to their | + | While the majority of proteins fold rapidly and spontaneously to their native states, the extracellular bacterial protease alpha-lytic protease (alphaLP) has a t(1/2) for folding of approximately 2,000 years, corresponding to a folding barrier of 30 kcal mol(-1). AlphaLP is synthesized as a pro-enzyme where its pro region (Pro) acts as a foldase to stabilize the transition state for the folding reaction. Pro also functions as a potent folding catalyst when supplied as a separate polypeptide chain, accelerating the rate of alphaLP folding by a factor of 3 x 10(9). In the absence of Pro, alphaLP folds only partially to a stable molten globule-like intermediate state. Addition of Pro to this intermediate leads to rapid formation of native alphaLP. Here we report the crystal structures of Pro and of the non-covalent inhibitory complex between Pro and native alphaLP. The C-shaped Pro surrounds the C-terminal beta-barrel domain of the folded protease, forming a large complementary interface. Regions of extensive hydration in the interface explain how Pro binds tightly to the native state, yet even more tightly to the folding transition state. Based on structural and functional data we propose that a specific structural element in alphaLP is largely responsible for the folding barrier and suggest how Pro can overcome this barrier. |
==About this Structure== | ==About this Structure== | ||
| - | 4PRO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Lysobacter_enzymogenes Lysobacter enzymogenes]. Full crystallographic information is available from [http:// | + | 4PRO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Lysobacter_enzymogenes Lysobacter enzymogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PRO OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Lysobacter enzymogenes]] | [[Category: Lysobacter enzymogenes]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Agard, D | + | [[Category: Agard, D A.]] |
[[Category: Mau, T.]] | [[Category: Mau, T.]] | ||
| - | [[Category: Rader, S | + | [[Category: Rader, S D.]] |
| - | [[Category: Sauter, N | + | [[Category: Sauter, N K.]] |
[[Category: foldase]] | [[Category: foldase]] | ||
[[Category: pro region]] | [[Category: pro region]] | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:14:05 2008'' |
Revision as of 17:14, 21 February 2008
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ALPHA-LYTIC PROTEASE COMPLEXED WITH PRO REGION
Overview
While the majority of proteins fold rapidly and spontaneously to their native states, the extracellular bacterial protease alpha-lytic protease (alphaLP) has a t(1/2) for folding of approximately 2,000 years, corresponding to a folding barrier of 30 kcal mol(-1). AlphaLP is synthesized as a pro-enzyme where its pro region (Pro) acts as a foldase to stabilize the transition state for the folding reaction. Pro also functions as a potent folding catalyst when supplied as a separate polypeptide chain, accelerating the rate of alphaLP folding by a factor of 3 x 10(9). In the absence of Pro, alphaLP folds only partially to a stable molten globule-like intermediate state. Addition of Pro to this intermediate leads to rapid formation of native alphaLP. Here we report the crystal structures of Pro and of the non-covalent inhibitory complex between Pro and native alphaLP. The C-shaped Pro surrounds the C-terminal beta-barrel domain of the folded protease, forming a large complementary interface. Regions of extensive hydration in the interface explain how Pro binds tightly to the native state, yet even more tightly to the folding transition state. Based on structural and functional data we propose that a specific structural element in alphaLP is largely responsible for the folding barrier and suggest how Pro can overcome this barrier.
About this Structure
4PRO is a Protein complex structure of sequences from Lysobacter enzymogenes. Full crystallographic information is available from OCA.
Reference
Structure of alpha-lytic protease complexed with its pro region., Sauter NK, Mau T, Rader SD, Agard DA, Nat Struct Biol. 1998 Nov;5(11):945-50. PMID:9808037
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