1by7
From Proteopedia
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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
Page seeded by OCA on Mon Nov 12 16:15:29 2007
