Structural studies of duck delta 1 and delta 2 crystallin suggest conformational changes occur during catalysis

Duck delta1 and delta2 crystallin are 94% identical in amino acid sequence, and while delta2 crystallin is the duck orthologue of argininosuccinate ly ase (ASL) and catalyzes the reversible breakdown of argininosuccinate to ar ginine and fumarate, the delta1 isoform is enzymatically inactive. The crys tal structures of wild type duck delta1 and delta2 crystallin have been sol ved at 2.2 and 2.3 Angstrom, resolution, respectively, and the refinement o f the turkey delta1 crystallin has been completed. These structures have be en compared with two mutant duck delta2 crystallin structures. Conformation al changes were observed in two regions of the N-terminal domain with intra species differences between the active and inactive isoforms localized to r esidues 23-32 and both intra- and interspecies differences localized to the loop of residues 74-89. As the residues implicated in the catalytic mechan ism of delta2/ASL are all conserved in delta1, 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 delta1 crystallin. T his anion, which appears to mimic the fumarate moiety of the argininosuccin ate substrate, induces a rigid body movement in domain 3 and a conformation al change in the loop of residues 280-290, which together would sequester t he substrate from the solvent. The duck delta1 crystallin structure suggest s that Ser 281, a residue strictly conserved in all members of the superfam ily, could be the catalytic acid in the delta2 crystallin/ASL enzymatic mec hanism.