1as4
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(New page: 200px<br /> <applet load="1as4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1as4, resolution 2.1Å" /> '''CLEAVED ANTICHYMOTRY...)
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Revision as of 13:55, 12 November 2007
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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 diseases 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 with ACT as ligand. 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
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