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1as4
From Proteopedia
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'''CLEAVED ANTICHYMOTRYPSIN A349R''' | '''CLEAVED ANTICHYMOTRYPSIN A349R''' | ||
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[[Category: Christianson, D W.]] | [[Category: Christianson, D W.]] | ||
[[Category: Lukacs, C M.]] | [[Category: Lukacs, C M.]] | ||
| - | [[Category: | + | [[Category: Antichymotrypsin]] |
| - | [[Category: | + | [[Category: Serine protease inhibitor]] |
| - | [[Category: | + | [[Category: Serpin]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:38:18 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 07:38, 2 May 2008
CLEAVED ANTICHYMOTRYPSIN A349R
Contents |
Overview
Expressed in a kinetically trapped folding state, a serpin couples the thermodynamic driving force of a massive beta-sheet rearrangement to the inhibition of a target protease. Hence, the serpin-protease interaction is the premier example of a "spring-loaded" protein-protein interaction. Amino acid substitutions in the hinge region of a serpin reactive loop can weaken the molecular spring, which converts the serpin from an inhibitor into a substrate. To probe the molecular basis of this conversion, we report the crystal structure of A349R antichymotrypsin in the reactive loop cleaved state at 2.1 A resolution. This amino acid substitution does not block the beta-sheet rearrangement despite the burial of R349 in the hydrophobic core of the cleaved serpin along with a salt-linked acetate ion. The inhibitory activity of this serpin variant is not obliterated; remarkably, its inhibitory properties are anion-dependent due to the creation of an anion-binding cavity in the cleaved serpin.
Disease
Known disease associated with this structure: Alpha-1-antichymotrypsin deficiency OMIM:[107280], Cerebrovascular disease, occlusive OMIM:[107280]
About this Structure
1AS4 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Engineering an anion-binding cavity in antichymotrypsin modulates the "spring-loaded" serpin-protease interaction., Lukacs CM, Rubin H, Christianson DW, Biochemistry. 1998 Mar 10;37(10):3297-304. PMID:9521649 Page seeded by OCA on Fri May 2 10:38:18 2008
