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PDBsum entry 3gcb
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Hydrolase PDB id
3gcb

 

 

 

 

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Contents
Protein chain
458 a.a. *
Ligands
SO4 ×5
GOL ×2
Waters ×421
* Residue conservation analysis
PDB id:
3gcb
Name: Hydrolase
Title: Gal6 (yeast bleomycin hydrolase) mutant c73a/deltak454
Structure: Gal6. Chain: a. Synonym: ybh, yeast bleomycin hydrolase. Engineered: yes. Mutation: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Cell_line: bl21. Gene: gal6c73adelk. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Hexamer (from PDB file)
Resolution:
1.87Å     R-factor:   0.173     R-free:   0.217
Authors: L.Joshua-Tor,W.Zheng,S.A.Johnston
Key ref:
W.Zheng et al. (1998). The unusual active site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase, and peptide ligase. Cell, 93, 103-109. PubMed id: 9546396 DOI: 10.1016/S0092-8674(00)81150-2
Date:
27-Feb-98     Release date:   21-Oct-98    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q01532  (BLH1_YEAST) -  Cysteine proteinase 1, mitochondrial from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Seq:
Struc: 		483 a.a.
458 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 7 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.4.22.40  - bleomycin hydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Inactivates bleomycin B2 (a cytotoxic glycometallopeptide) by hydrolysis of a carboxyamide bond of b-aminoalanine, but also shows general aminopeptidase activity. The specificity varies somewhat with source, but amino acid arylamides of Met, Leu and Ala are preferred.

 

 
DOI no: 10.1016/S0092-8674(00)81150-2 Cell 93:103-109 (1998)
PubMed id: 9546396  
 
 
The unusual active site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase, and peptide ligase.
W.Zheng, S.A.Johnston, L.Joshua-Tor.
 
  ABSTRACT  
 
The Gal6 protease is in a class of cysteine peptidases identified by their ability to inactivate the anti-cancer drug bleomycin. The protein forms a barrel structure with the active sites embedded in a channel as in the proteasome. In Gal6 the C termini lie in the active site clefts. We show that Gal6 acts as a carboxypeptidase on its C terminus to convert itself to an aminopeptidase and peptide ligase. The substrate specificity of the peptidase activity is determined by the position of the C terminus of Gal6 rather than the sequence of the substrate. We propose a model to explain these diverse activities and Gal6's singular ability to inactivate bleomycin.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. G450A Has a Different Processing Pattern from the Wild-Type ProteinAn electrospray mass spectrometry shows G450A protein cleaving either one or three residues of the C terminus. 		Figure 6.
Figure 6. Possible Mechanism of Bleomycin Hydrolysis by Bleomycin Hydrolase
 
  The above figures are reprinted by permission from Cell Press: Cell (1998, 93, 103-109) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18817889 C.R.Berkers, A.de Jong, H.Ovaa, and B.Rodenko (2009).
Transpeptidation and reverse proteolysis and their consequences for immunity.
  Int J Biochem Cell Biol, 41, 66-71.  
17937605 H.Jakubowski (2007).
The molecular basis of homocysteine thiolactone-mediated vascular disease.
  Clin Chem Lab Med, 45, 1704-1716.  
17391860 S.E.Montoya, E.Thiels, J.P.Card, and J.S.Lazo (2007).
Astrogliosis and behavioral changes in mice lacking the neutral cysteine protease bleomycin hydrolase.
  Neuroscience, 146, 890-900.  
16543139 H.R.Stennicke, and G.S.Salvesen (2006).
Chemical ligation--an unusual paradigm in protease inhibition.
  Mol Cell, 21, 727-728.  
16769724 J.Zimny, M.Sikora, A.Guranowski, and H.Jakubowski (2006).
Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase.
  J Biol Chem, 281, 22485-22492.  
16339904 D.Vivares, P.Arnoux, and D.Pignol (2005).
A papain-like enzyme at work: native and acyl-enzyme intermediate structures in phytochelatin synthesis.
  Proc Natl Acad Sci U S A, 102, 18848-18853.
PDB codes: 2btw 2bu3
14739292 T.Liu, B.Lu, I.Lee, G.Ondrovicová, E.Kutejová, and C.K.Suzuki (2004).
DNA and RNA binding by the mitochondrial lon protease is regulated by nucleotide and protein substrate.
  J Biol Chem, 279, 13902-13910.  
14621998 O.Vasiljeva, M.Dolinar, V.Turk, and B.Turk (2003).
Recombinant human cathepsin H lacking the mini chain is an endopeptidase.
  Biochemistry, 42, 13522-13528.  
12555812 H.Wang, and D.Ramotar (2002).
Cellular resistance to bleomycin in Saccharomyces cerevisiae is not affected by changes in bleomycin hydrolase levels.
  Biochem Cell Biol, 80, 789-796.  
11389845 A.Ferdous, F.Gonzalez, L.Sun, T.Kodadek, and S.A.Johnston (2001).
The 19S regulatory particle of the proteasome is required for efficient transcription elongation by RNA polymerase II.
  Mol Cell, 7, 981-991.  
10404591 P.A.O'Farrell, F.Gonzalez, W.Zheng, S.A.Johnston, and L.Joshua-Tor (1999).
Crystal structure of human bleomycin hydrolase, a self-compartmentalizing cysteine protease.
  Structure, 7, 619-627.
PDB codes: 1cb5 2cb5
  10595552 T.C.Cheng, V.Ramakrishnan, and S.I.Chan (1999).
Purification and characterization of a cobalt-activated carboxypeptidase from the hyperthermophilic archaeon Pyrococcus furiosus.
  Protein Sci, 8, 2474-2486.  
9846880 R.S.Bhatnagar, K.Fütterer, T.A.Farazi, S.Korolev, C.L.Murray, E.Jackson-Machelski, G.W.Gokel, J.I.Gordon, and G.Waksman (1998).
Structure of N-myristoyltransferase with bound myristoylCoA and peptide substrate analogs.
  Nat Struct Biol, 5, 1091-1097.
PDB code: 2nmt
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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