Structural highlights
Function
[ARLY2_ANAPL] Delta crystallin, the principal crystallin in embryonic lens, is found only in birds and reptiles. This protein also functions as an enzymatically active argininosuccinate lyase.[1] [2] [3] [4]
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 PubMed
Duck delta1 and delta2 crystallin are 94% identical in amino acid sequence, and while delta2 crystallin is the duck orthologue of argininosuccinate lyase (ASL) and catalyzes the reversible breakdown of argininosuccinate to arginine and fumarate, the delta1 isoform is enzymatically inactive. The crystal structures of wild type duck delta1 and delta2 crystallin have been solved at 2.2 and 2.3 A resolution, respectively, and the refinement of the turkey delta1 crystallin has been completed. These structures have been compared with two mutant duck delta2 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 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. 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 delta1 crystallin structure suggests that Ser 281, a residue strictly conserved in all members of the superfamily, could be the catalytic acid in the delta2 crystallin/ASL enzymatic mechanism.
Structural studies of duck delta 1 and delta 2 crystallin suggest conformational changes occur during catalysis.,Sampaleanu LM, Vallee F, Slingsby C, Howell PL Biochemistry. 2001 Mar 6;40(9):2732-42. PMID:11258884[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Vallee F, Turner MA, Lindley PL, Howell PL. Crystal structure of an inactive duck delta II crystallin mutant with bound argininosuccinate. Biochemistry. 1999 Feb 23;38(8):2425-34. PMID:10029536 doi:10.1021/bi982149h
- ↑ Sampaleanu LM, Yu B, Howell PL. Mutational analysis of duck delta 2 crystallin and the structure of an inactive mutant with bound substrate provide insight into the enzymatic mechanism of argininosuccinate lyase. J Biol Chem. 2002 Feb 8;277(6):4166-75. Epub 2001 Nov 6. PMID:11698398 doi:10.1074/jbc.M107465200
- ↑ Sampaleanu LM, Codding PW, Lobsanov YD, Tsai M, Smith GD, Horvatin C, Howell PL. Structural studies of duck delta2 crystallin mutants provide insight into the role of Thr161 and the 280s loop in catalysis. Biochem J. 2004 Dec 1;384(Pt 2):437-47. PMID:15320872 doi:10.1042/BJ20040656
- ↑ Abu-Abed M, Turner MA, Vallee F, Simpson A, Slingsby C, Howell PL. Structural comparison of the enzymatically active and inactive forms of delta crystallin and the role of histidine 91. Biochemistry. 1997 Nov 18;36(46):14012-22. PMID:9369472 doi:10.1021/bi971407s
- ↑ Sampaleanu LM, Vallee F, Slingsby C, Howell PL. Structural studies of duck delta 1 and delta 2 crystallin suggest conformational changes occur during catalysis. Biochemistry. 2001 Mar 6;40(9):2732-42. PMID:11258884
