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PDBsum entry 1jfv

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protein ligands metals links
Oxidoreductase PDB id
1jfv
Jmol
Contents
Protein chain
131 a.a. *
Ligands
LCP
Metals
__K
Waters ×125
* Residue conservation analysis
PDB id:
1jfv
Name: Oxidoreductase
Title: X-ray structure of oxidised c10s, c15a arsenate reductase from pi258
Structure: Arsenate reductase. Chain: a. Synonym: arsenical pump modifier. Engineered: yes. Mutation: yes
Source: Staphylococcus aureus. Organism_taxid: 1280. Gene: arsc. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.00Å     R-factor:   0.236     R-free:   0.286
Authors: I.Zegers,J.C.Martins,R.Willem,L.Wyns,J.Messens
Key ref:
I.Zegers et al. (2001). Arsenate reductase from S. aureus plasmid pI258 is a phosphatase drafted for redox duty. Nat Struct Biol, 8, 843-847. PubMed id: 11573087 DOI: 10.1038/nsb1001-843
Date:
22-Jun-01     Release date:   03-Oct-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0A006  (ARSC_STAAU) -  Protein ArsC
Seq:
Struc:
131 a.a.
131 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.1.3.48  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     peptidyl-tyrosine dephosphorylation   4 terms 
  Biochemical function     oxidoreductase activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1038/nsb1001-843 Nat Struct Biol 8:843-847 (2001)
PubMed id: 11573087  
 
 
Arsenate reductase from S. aureus plasmid pI258 is a phosphatase drafted for redox duty.
I.Zegers, J.C.Martins, R.Willem, L.Wyns, J.Messens.
 
  ABSTRACT  
 
Arsenate reductase (ArsC) from Staphylococcus aureus plasmid pI258 plays a role in bacterial heavy metal resistance and catalyzes the reduction of arsenate to arsenite. The structures of the oxidized and reduced forms of ArsC were solved. ArsC has the PTPase I fold typical for low molecular weight tyrosine phosphatases (LMW PTPases). Remarkably, kinetic experiments show that pI258 ArsC also catalyzes the tyrosine phosphatase reaction in addition to arsenate reduction. These results provide evidence that ArsC from pI258 evolved from LMW PTPase by the grafting of a redox function onto a pre-existing catalytic site and that its evolutionary origin is different from those of arsenate reductases from Escherichia coli plasmid R773 and from Saccharomyces cerevisiae. The mechanism proposed here for the catalysis of arsenate reduction by pI258 ArsC involves a nucleophilic attack by Cys 10 on arsenate, the formation of a covalent intermediate and the transport of oxidative equivalents by a disulfide cascade. The reaction is associated with major structural changes in the ArsC.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. The structure of pI258 ArsC. a, Overall structure of the reduced form of arsenate reductase. The catalytic site region is shown in red, and the part of the protein involved in the redox function in yellow. The area of ArsC corresponding to the Tyr binding site in LMW PTPase is shown in green. b, 2F[o] - F[c] electron density map in the region of the active site of the reduced form of ArsC at 1.1 resolution. The map shows a carbonate bound to the P-loop and the electron density for the Cys 82 sulfinic acid, and is contoured at 1.5 . c, 2F[o] - F[c] electron density map in the region of the Cys 82 -Cys 89 disulfide bond in the oxidized form of ArsC at 2.0 resolution. The map is contoured at 1.0 . d, The active site of the oxidized form of ArsC (ArsC-ox, orange) is superimposed on that of the reduced form of ArsC (ArsC-red, blue). For the structure of ArsC-red, the carbonate, Tris, Cys 82, Cys 89 and residues from a hydrophobic core surrounding Cys 89 are shown. For ArsC-ox, Cys 82 and Cys 89 and the perchlorate are shown. e, Mapping of ArsC-red residues whose amide correlation peaks either disappear (blue) or are significantly perturbed ( (1H) > 0.04 p.p.m. and (15N) > 0.27 p.p.m.; red) when 50 mM K[2]SO[4] is removed from the NMR solution by dialysis against phosphate only buffer. Secondary structure elements are highlighted in green (helices) and yellow (sheets). f, Superposition of the active site region of ArsC-red with a bound carbonate (blue) on the active site region of human LMW tyrosine phosphatase (green), including a 2-(N-morholino)ethanesulfonic acid (MES) molecule bound to the Tyr binding site. g, CPK model of ArsC-ox. Cys side chains are shown in yellow; side chains of hydrophobic residues, green; side chain oxygens of Asp and Glu, red; and side chains nitrogens of Lys and Arg, blue.
Figure 3.
Figure 3. Catalytic mechanism of pI258 ArsC. a, Reaction scheme for the reaction catalyzed by LMW PTPases14. b, Reaction scheme proposed for the reduction of arsenate by S. aureus pI258 ArsC. The reaction starts with a nucleophilic attack of Cys 10 on an arsenate, leading to the formation of a covalent intermediate. For the next steps, we propose a disulfide cascade that brings about the reduction of the arsenic (V) to arsenic (III). Cys 82 can attack Cys 10, forming an intermediate Cys 10 -Cys 82 disulfide bond. Cys 10 can donate an electron pair to the arsenic. Cys 89 can then attack Cys 82, regenerating Cys 10 and forming a Cys 82 -Cys 89 disulfide bond, as found in ArsC-ox.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 843-847) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19286650 E.Ordóñez, K.Van Belle, G.Roos, S.De Galan, M.Letek, J.A.Gil, L.Wyns, L.M.Mateos, and J.Messens (2009).
Arsenate reductase, mycothiol, and mycoredoxin concert thiol/disulfide exchange.
  J Biol Chem, 284, 15107-15116.  
19675666 G.Roos, N.Foloppe, K.Van Laer, L.Wyns, L.Nilsson, P.Geerlings, and J.Messens (2009).
How thioredoxin dissociates its mixed disulfide.
  PLoS Comput Biol, 5, e1000461.  
18785928 N.O.Kaakoush, M.Raftery, and G.L.Mendz (2008).
Molecular responses of Campylobacter jejuni to cadmium stress.
  FEBS J, 275, 5021-5033.  
17432936 D.Muller, C.Médigue, S.Koechler, V.Barbe, M.Barakat, E.Talla, V.Bonnefoy, E.Krin, F.Arsène-Ploetze, C.Carapito, M.Chandler, B.Cournoyer, S.Cruveiller, C.Dossat, S.Duval, M.Heymann, E.Leize, A.Lieutaud, D.Lièvremont, Y.Makita, S.Mangenot, W.Nitschke, P.Ortet, N.Perdrial, B.Schoepp, P.Siguier, D.D.Simeonova, Z.Rouy, B.Segurens, E.Turlin, D.Vallenet, A.Van Dorsselaer, S.Weiss, J.Weissenbach, M.C.Lett, A.Danchin, and P.N.Bertin (2007).
A tale of two oxidation states: bacterial colonization of arsenic-rich environments.
  PLoS Genet, 3, e53.  
17588128 N.O.Kaakoush, T.Sterzenbach, W.G.Miller, S.Suerbaum, and G.L.Mendz (2007).
Identification of disulfide reductases in Campylobacterales: a bioinformatics investigation.
  Antonie Van Leeuwenhoek, 92, 429-441.  
17521354 N.O.Kaakoush, Z.Kovach, and G.L.Mendz (2007).
Potential role of thiol:disulfide oxidoreductases in the pathogenesis of Helicobacter pylori.
  FEMS Immunol Med Microbiol, 50, 177-183.  
17303556 Y.Li, Y.Hu, X.Zhang, H.Xu, E.Lescop, B.Xia, and C.Jin (2007).
Conformational fluctuations coupled to the thiol-disulfide transfer between thioredoxin and arsenate reductase in Bacillus subtilis.
  J Biol Chem, 282, 11078-11083.
PDB codes: 2gzy 2gzz 2ipa
17008719 D.Tolkatchev, R.Shaykhutdinov, P.Xu, J.Plamondon, D.C.Watson, N.M.Young, and F.Ni (2006).
Three-dimensional structure and ligand interactions of the low molecular weight protein tyrosine phosphatase from Campylobacter jejuni.
  Protein Sci, 15, 2381-2394.
PDB code: 2gi4
16607668 G.Roos, S.Loverix, E.Brosens, K.Van Belle, L.Wyns, P.Geerlings, and J.Messens (2006).
The activation of electrophile, nucleophile and leaving group during the reaction catalysed by pI258 arsenate reductase.
  Chembiochem, 7, 981-989.  
16963640 L.Volpon, C.R.Young, A.Matte, and K.Gehring (2006).
NMR structure of the enzyme GatB of the galactitol-specific phosphoenolpyruvate-dependent phosphotransferase system and its interaction with GatA.
  Protein Sci, 15, 2435-2441.
PDB code: 1tvm
15890001 A.Salmeen, and D.Barford (2005).
Functions and mechanisms of redox regulation of cysteine-based phosphatases.
  Antioxid Redox Signal, 7, 560-577.  
16204540 E.Ordóñez, M.Letek, N.Valbuena, J.A.Gil, and L.M.Mateos (2005).
Analysis of genes involved in arsenic resistance in Corynebacterium glutamicum ATCC 13032.
  Appl Environ Microbiol, 71, 6206-6215.  
15691908 S.Silver, and L.T.Phung (2005).
Genes and enzymes involved in bacterial oxidation and reduction of inorganic arsenic.
  Appl Environ Microbiol, 71, 599-608.  
16372009 W.C.Nierman, A.Pain, M.J.Anderson, J.R.Wortman, H.S.Kim, J.Arroyo, M.Berriman, K.Abe, D.B.Archer, C.Bermejo, J.Bennett, P.Bowyer, D.Chen, M.Collins, R.Coulsen, R.Davies, P.S.Dyer, M.Farman, N.Fedorova, N.Fedorova, T.V.Feldblyum, R.Fischer, N.Fosker, A.Fraser, J.L.García, M.J.García, A.Goble, G.H.Goldman, K.Gomi, S.Griffith-Jones, R.Gwilliam, B.Haas, H.Haas, D.Harris, H.Horiuchi, J.Huang, S.Humphray, J.Jiménez, N.Keller, H.Khouri, K.Kitamoto, T.Kobayashi, S.Konzack, R.Kulkarni, T.Kumagai, A.Lafon, A.Lafton, J.P.Latgé, W.Li, A.Lord, C.Lu, W.H.Majoros, G.S.May, B.L.Miller, Y.Mohamoud, M.Molina, M.Monod, I.Mouyna, S.Mulligan, L.Murphy, S.O'Neil, I.Paulsen, M.A.Peñalva, M.Pertea, C.Price, B.L.Pritchard, M.A.Quail, E.Rabbinowitsch, N.Rawlins, M.A.Rajandream, U.Reichard, H.Renauld, G.D.Robson, S.Rodriguez de Córdoba, J.M.Rodríguez-Peña, C.M.Ronning, S.Rutter, S.L.Salzberg, M.Sanchez, J.C.Sánchez-Ferrero, D.Saunders, K.Seeger, R.Squares, S.Squares, M.Takeuchi, F.Tekaia, G.Turner, C.R.Vazquez de Aldana, J.Weidman, O.White, J.Woodward, J.H.Yu, C.Fraser, J.E.Galagan, K.Asai, M.Machida, N.Hall, B.Barrell, and D.W.Denning (2005).
Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus.
  Nature, 438, 1151-1156.  
16192272 X.Guo, Y.Li, K.Peng, Y.Hu, C.Li, B.Xia, and C.Jin (2005).
Solution structures and backbone dynamics of arsenate reductase from Bacillus subtilis: reversible conformational switch associated with arsenate reduction.
  J Biol Chem, 280, 39601-39608.
PDB codes: 1z2d 1z2e
15102337 A.Teplyakov, S.Pullalarevu, G.Obmolova, V.Doseeva, A.Galkin, O.Herzberg, M.Dauter, Z.Dauter, and G.L.Gilliland (2004).
Crystal structure of the YffB protein from Pseudomonas aeruginosa suggests a glutathione-dependent thiol reductase function.
  BMC Struct Biol, 4, 5.
PDB code: 1rw1
15159594 J.Messens, I.Van Molle, P.Vanhaesebrouck, K.Van Belle, K.Wahni, J.C.Martins, L.Wyns, and R.Loris (2004).
The structure of a triple mutant of pI258 arsenate reductase from Staphylococcus aureus and its 5-thio-2-nitrobenzoic acid adduct.
  Acta Crystallogr D Biol Crystallogr, 60, 1180-1184.
PDB codes: 1rxe 1rxi
15295115 S.DeMel, J.Shi, P.Martin, B.P.Rosen, and B.F.Edwards (2004).
Arginine 60 in the ArsC arsenate reductase of E. coli plasmid R773 determines the chemical nature of the bound As(III) product.
  Protein Sci, 13, 2330-2340.
PDB codes: 1s3c 1s3d 1sd8 1sd9 1sjz 1sk0 1sk1 1sk2
12949088 L.López-Maury, F.J.Florencio, and J.C.Reyes (2003).
Arsenic sensing and resistance system in the cyanobacterium Synechocystis sp. strain PCC 6803.
  J Bacteriol, 185, 5363-5371.  
12682056 N.Lah, J.Lah, I.Zegers, L.Wyns, and J.Messens (2003).
Specific potassium binding stabilizes pI258 arsenate reductase from Staphylococcus aureus.
  J Biol Chem, 278, 24673-24679.  
14617642 R.Li, J.D.Haile, and P.J.Kennelly (2003).
An arsenate reductase from Synechocystis sp. strain PCC 6803 exhibits a novel combination of catalytic characteristics.
  J Bacteriol, 185, 6780-6789.  
12711608 R.Mukhopadhyay, Y.Zhou, and B.P.Rosen (2003).
Directed evolution of a yeast arsenate reductase into a protein-tyrosine phosphatase.
  J Biol Chem, 278, 24476-24480.  
12829274 S.Silver (2003).
Bacterial silver resistance: molecular biology and uses and misuses of silver compounds.
  FEMS Microbiol Rev, 27, 341-353.  
12072565 J.Messens, J.C.Martins, K.Van Belle, E.Brosens, A.Desmyter, M.De Gieter, J.M.Wieruszeski, R.Willem, L.Wyns, and I.Zegers (2002).
All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade.
  Proc Natl Acad Sci U S A, 99, 8506-8511.
PDB codes: 1ljl 1lju 1lk0
12165430 R.Mukhopadhyay, B.P.Rosen, L.T.Phung, and S.Silver (2002).
Microbial arsenic: from geocycles to genes and enzymes.
  FEMS Microbiol Rev, 26, 311-325.  
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.