The C-terminus of human bleomycin hydrolase is required for protection against bleomycin-induced chromosomal damage.

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Lefterov IM, Koldamova RP, King J, Lazo JS

The C-terminus of human bleomycin hydrolase is required for protection against bleomycin-induced chromosomal damage.

Mutat Res. 1998 Oct 12;421(1):1-7.

PubMed ID

9748474 [ View in PubMed

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Abstract

Mammalian bleomycin hydrolases (BH) are enzymes with proven exopeptidase activity responsible for deamidation of the beta-aminoalanine moiety in bleomycin and are thought to limit the therapeutic efficacy of the drug. We have recently determined that the highly conserved BH-like domain in the C-terminus of human bleomycin hydrolase (hBH) is critical both for in vitro aminopeptidase and bleomycin metabolizing activities. To determine if hBH protects mammalian cells against bleomycin clastogenic effect, we transfected CHO cells with plasmids encoding hBH or C-terminal truncated forms and evaluated the level of chromatid breaks after bleomycin exposure. CHO cells expressing hBH had 50% less chromatid breaks after bleomycin treatment compared with mock transfected cells. The eight amino acid bleomycin hydrolase-like domain in the C-terminus, which does not contain any of the putative active site amino acids, was essential for protection against bleomycin induced chromatid breaks. These results demonstrate that intracellular hBH levels can influence the clastogenic action of bleomycin and that the C-terminus has a functional role in the biological activity of hBH.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Bleomycin	Bleomycin hydrolase	Protein	Humans	Unknown	Substrate	Details