Bleomycin hydrolase explained

Bleomycin hydrolase is an enzyme that in humans is encoded by the BLMH gene.^{[1] [2] [3]}

Bleomycin hydrolase (BMH) is a cytoplasmic cysteine peptidase that is highly conserved through evolution. Its biological function is hydrolysis of the reactive electrophile homocysteine thiolactone.^[4] Another of its activities is metabolic inactivation of the glycopeptide bleomycin (BLM), an essential component of combination chemotherapy regimens for cancer. The protein contains the signature active site residues of the cysteine protease papain superfamily.^[3]

Interactions

BLMH has been shown to interact with RPL29,^[5] RPL11,^[5] UBE2I^[6] and Amyloid precursor protein.^[7]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Ferrando AA, Velasco G, Campo E, Lopez-Otin C . Cloning and expression analysis of human bleomycin hydrolase, a cysteine proteinase involved in chemotherapy resistance. . Cancer Res. . 56 . 8 . 1746–50 . 1996 . 8620487 .
• Brömme D, Rossi AB, Smeekens SP . Human bleomycin hydrolase: molecular cloning, sequencing, functional expression, and enzymatic characterization. . Biochemistry . 35 . 21 . 6706–14 . 1996 . 8639621 . 10.1021/bi960092y . etal.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 . etal.
• Koldamova RP, Lefterov IM, Gadjeva VG, Lazo JS . Essential binding and functional domains of human bleomycin hydrolase. . Biochemistry . 37 . 8 . 2282–90 . 1998 . 9485374 . 10.1021/bi9722204 .
• Montoya SE, Aston CE, DeKosky ST . Bleomycin hydrolase is associated with risk of sporadic Alzheimer's disease. . Nat. Genet. . 18 . 3 . 211–2 . 1998 . 9500538 . 10.1038/ng0398-211 . 2940414 . etal.
• Zheng W, Johnston SA, Joshua-Tor L . The unusual active site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase, and peptide ligase. . Cell . 93 . 1 . 103–9 . 1998 . 9546396 . 10.1016/S0092-8674(00)81150-2 . free .
• Koldamova RP, Lefterov IM, DiSabella MT, Lazo JS . 2272861 . An evolutionarily conserved cysteine protease, human bleomycin hydrolase, binds to the human homologue of ubiquitin-conjugating enzyme 9. . Mol. Pharmacol. . 54 . 6 . 954–61 . 1999 . 9855622 . 10.1124/mol.54.6.954.
• Takeda A, Nonaka M, Ishikawa A, Higuchi D . Immunohistochemical localization of the neutral cysteine protease bleomycin hydrolase in human skin. . Arch. Dermatol. Res. . 291 . 4 . 238–40 . 1999 . 10335922 . 10.1007/s004030050400 . 10799259 .
• Koldamova RP, Lefterov IM, DiSabella MT . Human bleomycin hydrolase binds ribosomal proteins. . Biochemistry . 38 . 22 . 7111–7 . 1999 . 10353821 . 10.1021/bi990135l . etal.
• O'Farrell PA, Gonzalez F, Zheng W . Crystal structure of human bleomycin hydrolase, a self-compartmentalizing cysteine protease. . Structure . 7 . 6 . 619–27 . 1999 . 10404591 . 10.1016/S0969-2126(99)80083-5 . etal. free .
• Malherbe P, Faull RL, Richards JG . Regional and cellular distribution of bleomycin hydrolase mRNA in human brain: comparison between Alzheimer's diseased and control brains. . Neurosci. Lett. . 281 . 1 . 37–40 . 2000 . 10686410 . 10.1016/S0304-3940(00)00802-8 . 41562274 .
• Lefterov IM, Koldamova RP, Lazo JS . Human bleomycin hydrolase regulates the secretion of amyloid precursor protein. . FASEB J. . 14 . 12 . 1837–47 . 2000 . 10973933 . 10.1096/fj.99-0938com . free . 44302063 .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . etal. 2002PNAS...9916899M . free .
• Nivet-Antoine V, Coulhon MP, Le Denmat C . [Apolipoprotein E and bleomycin hydrolase. Polymorphisms: association with neurodegenerative diseases] . Ann. Biol. Clin. (Paris) . 61 . 1 . 61–7 . 2003 . 12604387 . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Rual JF, Venkatesan K, Hao T . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . etal. 2005Natur.437.1173R . 4427026 .

Notes and References

1. Ferrando AA, Pendas AM, Llano E, Velasco G, Lidereau R, Lopez-Otin C . Gene characterization, promoter analysis, and chromosomal localization of human bleomycin hydrolase . J Biol Chem . 272 . 52 . 33298–304 . January 1998 . 9407121 . 10.1074/jbc.272.52.33298 . free .
2. Montoya SE, Ferrell RE, Lazo JS . Genomic structure and genetic mapping of the human neutral cysteine protease bleomycin hydrolase . Cancer Res . 57 . 19 . 4191–5 . October 1997 . 9331073 .
3. Web site: Entrez Gene: BLMH bleomycin hydrolase.
4. Protective Mechanisms against Homocysteine Toxicity . Jarosław Zimny . Marta Sikora . Andrzej Guranowski . Hieronim Jakubowski . 2006 . The Journal of Biological Chemistry . 281 . 32 . 22485–22492 . 10.1074/jbc.M603656200 . 16769724 . free .
5. Koldamova . R P . Lefterov I M. DiSabella M T. Almonte C. Watkins S C. Lazo J S . June 1999 . Human bleomycin hydrolase binds ribosomal proteins . Biochemistry . 38 . 22 . 7111–7 . UNITED STATES. 0006-2960. 10353821 . 10.1021/bi990135l .
6. Koldamova . R P . Lefterov I M. DiSabella M T. Lazo J S . 2272861 . December 1998 . An evolutionarily conserved cysteine protease, human bleomycin hydrolase, binds to the human homologue of ubiquitin-conjugating enzyme 9 . Mol. Pharmacol. . 54 . 6 . 954–61 . UNITED STATES. 0026-895X. 9855622 . 10.1124/mol.54.6.954 .
7. 10.1096/fj.99-0938com . Lefterov . I M . Koldamova R P. Lazo J S . September 2000 . Human bleomycin hydrolase regulates the secretion of amyloid precursor protein . FASEB J. . 14 . 12 . 1837–47 . UNITED STATES. free . 0892-6638. 10973933 . 44302063 .