Catalytic domain, repeat 2, of yeast tyrosyl-DNA phosphodiesterase
Catalytic domain, repeat 2, of yeast tyrosyl-DNA phosphodiesterase (yTdp1, EC 3.1.4.-). yTdp1 is involved in the repair of topoisomerase I DNA lesions by hydrolyzing the topoisomerase from the 3'-end of the DNA during double-strand break repair. Unlike human Tdp1 whose substrate-binding pocket can accommodate a fairly large topoisomerase I peptide fragment, yTdp1 has a preference for substrates containing one to four amino acid residues. The monomeric yTdp1 contains two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Like other PLD enzymes, yTdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way.
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