1AS4

CLEAVED ANTICHYMOTRYPSIN A349R

Summary for 1AS4

• Entry DOI: 10.2210/pdb1as4/pdb
• Descriptor: ANTICHYMOTRYPSIN, ACETATE ION, ... (4 entities in total)
• Functional Keywords: serpin, serine protease inhibitor, antichymotrypsin
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P01011 P01011
• Total number of polymer chains: 2
• Total formula weight: 42930.19

Authors

Lukacs, C.M.,Christianson, D.W. (deposition date: 1997-08-12, release date: 1998-02-25, Last modification date: 2024-02-07)

Primary citation

Lukacs, C.M.,Rubin, H.,Christianson, D.W.
Engineering an anion-binding cavity in antichymotrypsin modulates the "spring-loaded" serpin-protease interaction.
Biochemistry, 37:3297-3304, 1998

PubMed Abstract: 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.

PubMed: 9521649
DOI: 10.1021/bi972359e

Experimental method

X-RAY DIFFRACTION (2.1 Å)