1by7
From Proteopedia
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'''HUMAN PLASMINOGEN ACTIVATOR INHIBITOR-2. LOOP (66-98) DELETION MUTANT''' | '''HUMAN PLASMINOGEN ACTIVATOR INHIBITOR-2. LOOP (66-98) DELETION MUTANT''' | ||
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[[Category: King, G C.]] | [[Category: King, G C.]] | ||
[[Category: Mabbutt, B C.]] | [[Category: Mabbutt, B C.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 12:06:31 2008'' | |
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Revision as of 09:06, 2 May 2008
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 Page seeded by OCA on Fri May 2 12:06:31 2008
