Structural Studies of Duck δ1 and δ2 Crystallin Suggest Conformational Changes Occur during Catalysis,

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Abstract
Duck δ1 and δ2 crystallin are 94% identical in amino acid sequence, and while δ2 crystallin is the duck orthologue of argininosuccinate lyase (ASL) and catalyzes the reversible breakdown of argininosuccinate to arginine and fumarate, the δ1 isoform is enzymatically inactive. The crystal structures of wild type duck δ1 and δ2 crystallin have been solved at 2.2 and 2.3 Å resolution, respectively, and the refinement of the turkey δ1 crystallin has been completed. These structures have been compared with two mutant duck δ2 crystallin structures. Conformational changes were observed in two regions of the N-terminal domain with intraspecies differences between the active and inactive isoforms localized to residues 23−32 and both intra- and interspecies differences localized to the loop of residues 74−89. As the residues implicated in the catalytic mechanism of δ2/ASL are all conserved in δ1, the amino acid substitutions in these two regions are hypothesized to be critical for substrate binding. A sulfate anion was found in the active site of duck δ1 crystallin. This anion, which appears to mimic the fumarate moiety of the argininosuccinate substrate, induces a rigid body movement in domain 3 and a conformational change in the loop of residues 280−290, which together would sequester the substrate from the solvent. The duck δ1 crystallin structure suggests that Ser 281, a residue strictly conserved in all members of the superfamily, could be the catalytic acid in the δ2 crystallin/ASL enzymatic mechanism.

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