This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1as4
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | Expressed in a kinetically trapped folding state, a serpin couples the | + | 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== | ==Disease== | ||
| Line 16: | Line 16: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Christianson, D | + | [[Category: Christianson, D W.]] |
| - | [[Category: Lukacs, C | + | [[Category: Lukacs, C M.]] |
[[Category: ACT]] | [[Category: ACT]] | ||
[[Category: antichymotrypsin]] | [[Category: antichymotrypsin]] | ||
| Line 23: | Line 23: | ||
[[Category: serpin]] | [[Category: serpin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:47:43 2008'' |
Revision as of 09:47, 21 February 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 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 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
Page seeded by OCA on Thu Feb 21 11:47:43 2008
