From Proteopedia
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| - | [[Image:1jvq.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1jvq.png|left|200px]] |
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| | {{STRUCTURE_1jvq| PDB=1jvq | SCENE= }} | | {{STRUCTURE_1jvq| PDB=1jvq | SCENE= }} |
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| - | '''Crystal structure at 2.6A of the ternary complex between antithrombin, a P14-P8 reactive loop peptide, and an exogenous tetrapeptide'''
| + | ===Crystal structure at 2.6A of the ternary complex between antithrombin, a P14-P8 reactive loop peptide, and an exogenous tetrapeptide=== |
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| - | ==Overview==
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| - | Many of the late-onset dementias, including Alzheimer's disease and the prion encephalopathies, arise from the aberrant aggregation of individual proteins. The serpin family of serine protease inhibitors provides a well-defined structural example of such pathological aggregation, as its mutant variants readily form long-chain polymers, resulting in diseases ranging from thrombosis to dementia. The intermolecular linkages result from the insertion of the reactive site loop of one serpin molecule into the middle strand (s4A) position of the A beta-sheet of another molecule. We define here the structural requirements for small peptides to competitively bind to and block the s4A position to prevent this intermolecular linkage and polymerisation. The entry and anchoring of blocking-peptides is facilitated by the presence of a threonine which inserts into the site equivalent to P8 of s4A. But the critical requirement for small blocking-peptides is demonstrated in crystallographic structures of the complexes formed with selected tri- and tetrapeptides. These structures indicate that the binding is primarily due to the insertion of peptide hydrophobic side-chains into the P4 and P6 sites of s4A. The findings allow the rational design of synthetic blocking-peptides small enough to be suitable for mimetic design. This is demonstrated here with a tetrapeptide that preferentially blocks the polymerisation of a pathologically unstable serpin commonly present in people of European descent.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_15342247}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15342247 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15342247}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Beta-barrell]] | | [[Category: Beta-barrell]] |
| | [[Category: Loop-sheet polymer]] | | [[Category: Loop-sheet polymer]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 21:59:03 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 21:01:12 2008'' |
Revision as of 18:01, 1 July 2008
Template:STRUCTURE 1jvq
Crystal structure at 2.6A of the ternary complex between antithrombin, a P14-P8 reactive loop peptide, and an exogenous tetrapeptide
Template:ABSTRACT PUBMED 15342247
About this Structure
1JVQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
How small peptides block and reverse serpin polymerisation., Zhou A, Stein PE, Huntington JA, Sivasothy P, Lomas DA, Carrell RW, J Mol Biol. 2004 Sep 17;342(3):931-41. PMID:15342247
Page seeded by OCA on Tue Jul 1 21:01:12 2008
