4caa
CLEAVED ANTICHYMOTRYPSIN T345RCLEAVED ANTICHYMOTRYPSIN T345R
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedExpressed 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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