IntEnz

EC 3.4.22.40 - Bleomycin hydrolase

IntEnz Enzyme Nomenclature
EC 3.4.22.40

Names

Reaction

• Inactivates bleomycin B2 (a cytotoxic glycometallopeptide) by hydrolysis of a carboxyamide bond of β-aminoalanine, but also shows general aminopeptidase activity. The specificity varies somewhat with source, but amino acid arylamides of Met, Leu and Ala are preferred [1].

Comments:

The molecule is a homohexamer in which the monomers have a papain-like tertiary structure (in peptidase family C1). The active sites are on the walls of a central channel through the molecule, and access of substrate molecules to them is obstructed by this and by the C-terminus of each polypeptide chain [3]. Bleomycin can scarcely be the natural substrate, and there are reports of limited endopeptidase activity. Known from bacteria as well as eukaryotic organisms. Hydrolase H from chicken muscle has many similarities to bleomycin hydrolase, but hydrolyses Ph-CO-Arg-2-naphthylamine as well as aminopeptidase substrates [2].

Links to other databases

References

1. Brömme, D., Rossi, A.B., Smeekens, S.P., Anderson, D.C. and Payan, D.G.
   Human bleomycin hydrolase: molecular cloning, sequencing, functional expression, and enzymatic characterization.
   Biochemistry 35: 6706-6714 (1996). [PMID: 8639621]
2. Adachi, H., Tsujimoto, M., Fukasawa, M., Sato, Y., Arai, H., Inoue, K. and Nishimura, T.
   cDNA cloning and expression of chicken aminopeptidase H, possessing endopeptidase as well as aminopeptidase activity.
   Eur. J. Biochem. 245: 283-288 (1997). [PMID: 9151954]
3. Zheng, W., Johnston, S.A. and Joshua-Tor, L.
   The unusual active site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase, and peptide ligase.
   Cell 93: 103-109 (1998). [PMID: 9546396]
4. Mistou, M.Y. and Gripon, J.C.
   Catalytic properties of the cysteine aminopeptidase PepC, a bacterial bleomycin hydrolase.
   Biochim. Biophys. Acta 1383: 63-70 (1998). [PMID: 9546047]

[EC 3.4.22.40 created 2000]