1as4

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[[Image:1as4.jpg|left|200px]]
[[Image:1as4.jpg|left|200px]]
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{{Structure
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|PDB= 1as4 |SIZE=350|CAPTION= <scene name='initialview01'>1as4</scene>, resolution 2.1&Aring;
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The line below this paragraph, containing "STRUCTURE_1as4", creates the "Structure Box" on the page.
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|GENE= ACT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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{{STRUCTURE_1as4| PDB=1as4 | SCENE= }}
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1as4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1as4 OCA], [http://www.ebi.ac.uk/pdbsum/1as4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1as4 RCSB]</span>
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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.]]
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[[Category: antichymotrypsin]]
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[[Category: Antichymotrypsin]]
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[[Category: serine protease inhibitor]]
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[[Category: Serine protease inhibitor]]
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[[Category: serpin]]
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[[Category: Serpin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:38:18 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:46:30 2008''
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Revision as of 07:38, 2 May 2008

Template:STRUCTURE 1as4

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

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