PDBsum entry 1gcb

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DNA-binding protein PDB id
Protein chain
452 a.a. *
SO4 ×3
_HG ×4
Waters ×238
* Residue conservation analysis
PDB id:
Name: DNA-binding protein
Title: Gal6, yeast bleomycin hydrolase DNA-binding protease (thiol)
Structure: Gal6 hg (emts) derivative. Chain: a. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Strain: sc277. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932
Biol. unit: Hexamer (from PQS)
2.20Å     R-factor:   0.209     R-free:   0.274
Authors: L.Joshua-Tor,H.E.Xu,S.A.Johnston,D.C.Rees
Key ref: L.Joshua-Tor et al. (1995). Crystal structure of a conserved protease that binds DNA: the bleomycin hydrolase, Gal6. Science, 269, 945-950. PubMed id: 7638617 DOI: 10.1126/science.7638617
18-Jul-95     Release date:   15-Oct-95    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q01532  (BLH1_YEAST) -  Cysteine proteinase 1, mitochondrial
483 a.a.
452 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 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.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     response to antibiotic   4 terms 
  Biochemical function     RNA polymerase II core promoter proximal region sequence-specific DNA binding     9 terms  


DOI no: 10.1126/science.7638617 Science 269:945-950 (1995)
PubMed id: 7638617  
Crystal structure of a conserved protease that binds DNA: the bleomycin hydrolase, Gal6.
L.Joshua-Tor, H.E.Xu, S.A.Johnston, D.C.Rees.
Bleomycin hydrolase is a cysteine protease that hydrolyzes the anticancer drug bleomycin. The homolog in yeast, Gal6, has recently been identified and found to bind DNA and to act as a repressor in the Gal4 regulatory system. The crystal structure of Gal6 at 2.2 A resolution reveals a hexameric structure with a prominent central channel. The papain-like active sites are situated within the central channel, in a manner resembling the organization of active sites in the proteasome. The Gal6 channel is lined with 60 lysine residues from the six subunits, suggesting a role in DNA binding. The carboxyl-terminal arm of Gal6 extends into the active site cleft and may serve a regulatory function. Rather than each residing in distinct, separable domains, the protease and DNA-binding activities appear structurally intertwined in the hexamer, implying a coupling of these two activities.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20360845 R.Lindsey, Y.Ha, and M.Momany (2010).
A septin from the filamentous fungus A. nidulans induces atypical pseudohyphae in the budding yeast S. cerevisiae.
  PLoS One, 5, e9858.  
18817889 C.R.Berkers, Jong, H.Ovaa, and B.Rodenko (2009).
Transpeptidation and reverse proteolysis and their consequences for immunity.
  Int J Biochem Cell Biol, 41, 66-71.  
18596064 D.R.Arnett, J.L.Jennings, D.L.Tabb, A.J.Link, and P.A.Weil (2008).
A proteomics analysis of yeast Mot1p protein-protein associations: insights into mechanism.
  Mol Cell Proteomics, 7, 2090-2106.  
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.  
14694194 M.Zhu, F.Shao, R.W.Innes, J.E.Dixon, and Z.Xu (2004).
The crystal structure of Pseudomonas avirulence protein AvrPphB: a papain-like fold with a distinct substrate-binding site.
  Proc Natl Acad Sci U S A, 101, 302-307.
PDB code: 1ukf
14576278 A.Sickmann, J.Reinders, Y.Wagner, C.Joppich, R.Zahedi, H.E.Meyer, B.Schönfisch, I.Perschil, A.Chacinska, B.Guiard, P.Rehling, N.Pfanner, and C.Meisinger (2003).
The proteome of Saccharomyces cerevisiae mitochondria.
  Proc Natl Acad Sci U S A, 100, 13207-13212.  
12554931 D.Turk, and G.Guncar (2003).
Lysosomal cysteine proteases (cathepsins): promising drug targets.
  Acta Crystallogr D Biol Crystallogr, 59, 203-213.  
12692242 M.Dimitrova, I.Imbert, M.P.Kieny, and C.Schuster (2003).
Protein-protein interactions between hepatitis C virus nonstructural proteins.
  J Virol, 77, 5401-5414.  
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.  
12857904 R.Perera, C.Navaratnarajah, and R.J.Kuhn (2003).
A heterologous coiled coil can substitute for helix I of the Sindbis virus capsid protein.
  J Virol, 77, 8345-8353.  
11980710 B.Franzetti, G.Schoehn, J.F.Hernandez, M.Jaquinod, R.W.Ruigrok, and G.Zaccai (2002).
Tetrahedral aminopeptidase: a novel large protease complex from archaea.
  EMBO J, 21, 2132-2138.  
16233174 M.Sugiyama, and T.Kumagai (2002).
Molecular and structural biology of bleomycin and its resistance determinants.
  J Biosci Bioeng, 93, 105-116.  
12124252 P.A.De-Alarcón, A.Pascual-Montano, A.Gupta, and J.M.Carazo (2002).
Modeling shape and topology of low-resolution density maps of biological macromolecules.
  Biophys J, 83, 619-632.  
11814340 T.R.Pray, K.K.Reiling, B.G.Demirjian, and C.S.Craik (2002).
Conformational change coupling the dimerization and activation of KSHV protease.
  Biochemistry, 41, 1474-1482.  
11726493 D.Turk, V.Janjić, I.Stern, M.Podobnik, D.Lamba, S.W.Dahl, C.Lauritzen, J.Pedersen, V.Turk, and B.Turk (2001).
Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases.
  EMBO J, 20, 6570-6582.
PDB code: 1k3b
11063501 D.H.Yun, J.Y.Chung, Y.B.Chung, Y.Y.Bahk, S.Y.Kang, Y.Kong, and S.Y.Cho (2000).
Structural and immunological characteristics of a 28-kilodalton cruzipain-like cysteine protease of Paragonimus westermani expressed in the definitive host stage.
  Clin Diagn Lab Immunol, 7, 932-939.  
10954757 E.W.Wang, B.M.Kessler, A.Borodovsky, B.F.Cravatt, M.Bogyo, H.L.Ploegh, and R.Glas (2000).
Integration of the ubiquitin-proteasome pathway with a cytosolic oligopeptidase activity.
  Proc Natl Acad Sci U S A, 97, 9990-9995.  
11114201 X.Du, I.G.Choi, R.Kim, W.Wang, J.Jancarik, H.Yokota, and S.H.Kim (2000).
Crystal structure of an intracellular protease from Pyrococcus horikoshii at 2-A resolution.
  Proc Natl Acad Sci U S A, 97, 14079-14084.
PDB code: 1g2i
  10518749 C.P.Ponting, and M.J.Pallen (1999).
beta-propeller repeats and a PDZ domain in the tricorn protease: predicted self-compartmentalisation and C-terminal polypeptide-binding strategies of substrate selection.
  FEMS Microbiol Lett, 179, 447-451.  
10200176 D.K.Nägler, W.Tam, A.C.Storer, J.C.Krupa, J.S.Mort, and R.Ménard (1999).
Interdependency of sequence and positional specificities for cysteine proteases of the papain family.
  Biochemistry, 38, 4868-4874.  
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
10353821 R.P.Koldamova, I.M.Lefterov, M.T.DiSabella, C.Almonte, S.C.Watkins, and J.S.Lazo (1999).
Human bleomycin hydrolase binds ribosomal proteins.
  Biochemistry, 38, 7111-7117.  
9818937 L.A.Farrer, C.R.Abraham, J.L.Haines, E.A.Rogaeva, Y.Song, W.T.McGraw, N.Brindle, S.Premkumar, W.K.Scott, L.H.Yamaoka, A.M.Saunders, A.D.Roses, S.A.Auerbach, S.Sorbi, R.Duara, M.A.Pericak-Vance, and P.H.St George-Hyslop (1998).
Association between bleomycin hydrolase and Alzheimer's disease in caucasians.
  Ann Neurol, 44, 808-811.  
  9521122 M.Gerstein, and M.Levitt (1998).
Comprehensive assessment of automatic structural alignment against a manual standard, the scop classification of proteins.
  Protein Sci, 7, 445-456.  
9485374 R.P.Koldamova, I.M.Lefterov, V.G.Gadjeva, and J.S.Lazo (1998).
Essential binding and functional domains of human bleomycin hydrolase.
  Biochemistry, 37, 2282-2290.  
9500538 S.E.Montoya, C.E.Aston, S.T.DeKosky, M.I.Kamboh, J.S.Lazo, and R.E.Ferrell (1998).
Bleomycin hydrolase is associated with risk of sporadic Alzheimer's disease.
  Nat Genet, 18, 211-212.  
9476896 W.Baumeister, J.Walz, F.Zühl, and E.Seemüller (1998).
The proteasome: paradigm of a self-compartmentalizing protease.
  Cell, 92, 367-380.  
  9584198 W.Zheng, and S.A.Johnston (1998).
The nucleic acid binding activity of bleomycin hydrolase is involved in bleomycin detoxification.
  Mol Cell Biol, 18, 3580-3585.  
9546396 W.Zheng, S.A.Johnston, and L.Joshua-Tor (1998).
The unusual active site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase, and peptide ligase.
  Cell, 93, 103-109.
PDB codes: 1a6r 3gcb
9357316 A.Lupas, J.M.Flanagan, T.Tamura, and W.Baumeister (1997).
Self-compartmentalizing proteases.
  Trends Biochem Sci, 22, 399-404.  
9390550 C.N.Larsen, and D.Finley (1997).
Protein translocation channels in the proteasome and other proteases.
  Cell, 91, 431-434.  
9074757 H.A.Chapman, R.J.Riese, and G.P.Shi (1997).
Emerging roles for cysteine proteases in human biology.
  Annu Rev Physiol, 59, 63-88.  
9659903 J.Walz, T.Tamura, N.Tamura, R.Grimm, W.Baumeister, and A.J.Koster (1997).
Tricorn protease exists as an icosahedral supermolecule in vivo.
  Mol Cell, 1, 59-65.  
9150143 W.Ward, L.Alvarado, N.D.Rawlings, J.C.Engel, C.Franklin, and J.H.McKerrow (1997).
A primitive enzyme for a primitive cell: the protease required for excystation of Giardia.
  Cell, 89, 437-444.  
8639621 D.Brömme, A.B.Rossi, S.P.Smeekens, D.C.Anderson, and D.G.Payan (1996).
Human bleomycin hydrolase: molecular cloning, sequencing, functional expression, and enzymatic characterization.
  Biochemistry, 35, 6706-6714.  
8718865 Z.Pei, and S.M.Sebti (1996).
Cys102 and His398 are required for bleomycin-inactivating activity but not for hexamer formation of yeast bleomycin hydrolase.
  Biochemistry, 35, 10751-10756.  
8574578 Z.Kelman, J.Finkelstein, and M.O'Donnell (1995).
Protein structure. Why have six-fold symmetry?
  Curr Biol, 5, 1239-1242.  
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 code is shown on the right.