1by7
From Proteopedia
(New page: 200px<br /> <applet load="1by7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1by7, resolution 2.0Å" /> '''HUMAN PLASMINOGEN AC...) |
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| - | [[Image:1by7.gif|left|200px]]<br /> | + | [[Image:1by7.gif|left|200px]]<br /><applet load="1by7" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1by7" size=" | + | |
caption="1by7, resolution 2.0Å" /> | caption="1by7, resolution 2.0Å" /> | ||
'''HUMAN PLASMINOGEN ACTIVATOR INHIBITOR-2. LOOP (66-98) DELETION MUTANT'''<br /> | '''HUMAN PLASMINOGEN ACTIVATOR INHIBITOR-2. LOOP (66-98) DELETION MUTANT'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Plasminogen activator inhibitor 2 (PAI-2) is a member of the | + | BACKGROUND: Plasminogen activator inhibitor 2 (PAI-2) is a member of the serpin family of protease inhibitors that function via a dramatic structural change from a native, stressed state to a relaxed form. This transition is mediated by a segment of the serpin termed the reactive centre loop (RCL); the RCL is cleaved on interaction with the protease and becomes inserted into betasheet A of the serpin. Major questions remain as to what factors facilitate this transition and how they relate to protease inhibition. RESULTS: The crystal structure of a mutant form of human PAI-2 in the stressed state has been determined at 2.0 A resolution. The RCL is completely disordered in the structure. An examination of polar residues that are highly conserved across all serpins identifies functionally important regions. A buried polar cluster beneath betasheet A (the so-called 'shutter' region) is found to stabilise both the stressed and relaxed forms via a rearrangement of hydrogen bonds. CONCLUSIONS: A statistical analysis of interstrand interactions indicated that the shutter region can be used to discriminate between inhibitory and non-inhibitory serpins. This analysis implied that insertion of the RCL into betasheet A up to residue P8 is important for protease inhibition and hence the structure of the complex formed between the serpin and the target protease. |
==About this Structure== | ==About this Structure== | ||
| - | 1BY7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1BY7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BY7 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Curmi, P | + | [[Category: Curmi, P M.G.]] |
| - | [[Category: Harrop, S | + | [[Category: Harrop, S J.]] |
| - | [[Category: King, G | + | [[Category: King, G C.]] |
| - | [[Category: Mabbutt, B | + | [[Category: Mabbutt, B C.]] |
[[Category: serpin]] | [[Category: serpin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:00:23 2008'' |
Revision as of 10:00, 21 February 2008
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HUMAN PLASMINOGEN ACTIVATOR INHIBITOR-2. LOOP (66-98) DELETION MUTANT
Overview
BACKGROUND: Plasminogen activator inhibitor 2 (PAI-2) is a member of the serpin family of protease inhibitors that function via a dramatic structural change from a native, stressed state to a relaxed form. This transition is mediated by a segment of the serpin termed the reactive centre loop (RCL); the RCL is cleaved on interaction with the protease and becomes inserted into betasheet A of the serpin. Major questions remain as to what factors facilitate this transition and how they relate to protease inhibition. RESULTS: The crystal structure of a mutant form of human PAI-2 in the stressed state has been determined at 2.0 A resolution. The RCL is completely disordered in the structure. An examination of polar residues that are highly conserved across all serpins identifies functionally important regions. A buried polar cluster beneath betasheet A (the so-called 'shutter' region) is found to stabilise both the stressed and relaxed forms via a rearrangement of hydrogen bonds. CONCLUSIONS: A statistical analysis of interstrand interactions indicated that the shutter region can be used to discriminate between inhibitory and non-inhibitory serpins. This analysis implied that insertion of the RCL into betasheet A up to residue P8 is important for protease inhibition and hence the structure of the complex formed between the serpin and the target protease.
About this Structure
1BY7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of plasminogen activator inhibitor 2 at 2.0 A resolution: implications for serpin function., Harrop SJ, Jankova L, Coles M, Jardine D, Whittaker JS, Gould AR, Meister A, King GC, Mabbutt BC, Curmi PM, Structure. 1999 Jan 15;7(1):43-54. PMID:10368272
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