Catalytic domain, repeat 1, of Deoxyribonuclease II beta and similar proteins
Catalytic domain, repeat 1, of Deoxyribonuclease II beta (DNase II beta, EC 3.1.22.1), also known as DNase II-like acid DNase (DLAD), and similar proteins. DNase II is a monomeric nuclease that contains two copies of a variant HKD motif, where the aspartic acid residue is not conserved. The HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) characterizes the phospholipase D (PLD, EC 3.1.4.4) superfamily. The catalytic center of DNase II is formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way. Members of this family are mainly found in metazoans, and vertebrate proteins have been further classified into DNase II alpha and beta. DNase II beta, or DLAD, is a novel mammalian divalent cation-independent endonuclease with homology to DNase II alpha. It is highly expressed in the eye lens and in salivary glands and is responsible for the degradation of nuclear DNA during lens cell differentiation. DLAD mainly exists as a cytoplasmic protein and cleaves DNA to produce 3'-phosphoryl/5'-hydroxyl ends. Like DNase II alpha, DLAD is active under acidic conditions with maximum activity at pH 5.2. Aurintricarboxylic acid and Zn2+ are effective inhibitors of DLAD activity. Mice deficient in DLAD develop cataracts as they are unable to degrade DNA during differentiation of the lens cells.
Comment:Based on similarity with phospholipase D, which functions as a bi-lobed monomer with two catalytic domains. Each domain carries one copy of the conserved HKD motif and two domains form a single active site.
Comment:The HKD signature motif (expanded to H-x-K-x(4)-D-x(6)-G-S-x-N, where x represents any amino acid residue) characterizes the PLD superfamily. The DNase II subfamily carries a variant HKD motif.
Comment:Most residues in the HKD motif are part of the active site.
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