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PDBsum entry 1ljl
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protein metals links
Oxidoreductase PDB id
1ljl

 

 

 

 

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Contents
Protein chain
130 a.a. *
Metals
__K
Waters ×100
* Residue conservation analysis
PDB id:
1ljl
Name: Oxidoreductase
Title: Wild type pi258 s. Aureus arsenate reductase
Structure: Arsenate reductase. Chain: a. Synonym: arsenical pump modifier. Engineered: yes. Other_details: reduced
Source: Staphylococcus aureus. Organism_taxid: 1280. Gene: arsc. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.01Å     R-factor:   0.214     R-free:   0.259
Authors: J.Messens,J.C.Martins,K.Van Belle,E.Brosens,A.Desmyter,M.De Gieter, J.M.Wieruszeski,R.Willem,L.Wyns,I.Zegers
Key ref:
J.Messens et al. (2002). All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade. Proc Natl Acad Sci U S A, 99, 8506-8511. PubMed id: 12072565 DOI: 10.1073/pnas.132142799
Date:
21-Apr-02     Release date:   07-Aug-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0A006  (ARSC_STAAU) -  Arsenate reductase from Staphylococcus aureus
Seq:
Struc: 		131 a.a.
130 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.20.4.4  - arsenate reductase (thioredoxin).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: arsenate + [thioredoxin]-dithiol + H+ = arsenite + [thioredoxin]- disulfide + H2O
arsenate
 + [thioredoxin]-dithiol
 + H(+)
 = arsenite
 + [thioredoxin]- disulfide
 + H2O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1073/pnas.132142799 Proc Natl Acad Sci U S A 99:8506-8511 (2002)
PubMed id: 12072565  
 
 
All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade.
J.Messens, J.C.Martins, K.Van Belle, E.Brosens, A.Desmyter, M.De Gieter, J.M.Wieruszeski, R.Willem, L.Wyns, I.Zegers.
 
  ABSTRACT  
 
The mechanism of pI258 arsenate reductase (ArsC) catalyzed arsenate reduction, involving its P-loop structural motif and three redox active cysteines, has been unraveled. All essential intermediates are visualized with x-ray crystallography, and NMR is used to map dynamic regions in a key disulfide intermediate. Steady-state kinetics of ArsC mutants gives a view of the crucial residues for catalysis. ArsC combines a phosphatase-like nucleophilic displacement reaction with a unique intramolecular disulfide bond cascade. Within this cascade, the formation of a disulfide bond triggers a reversible "conformational switch" that transfers the oxidative equivalents to the surface of the protein, while releasing the reduced substrate.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. (A) Scheme of the reaction mechanism of pI258 ArsC. (1) The nucleophilic attack of the thiol of Cys-10; (2) the formation of a covalent Cys-10-HAsO[ - ]intermediate; (3) the nucleophilic attack of the thiol of Cys-82 with arsenite release; (4) the formation of a Cys-10-Cys-82 intermediate and the nucleophilic attack of the thiol of Cys-89; (5) the formation of a Cys-82-Cys-89 disulfide. (B-F) A stereo view of the 2F[o] F[c] electron density maps contoured at 1.0 placed next to its corresponding reaction step in A. (B) The P-loop (residues 10-17) in the structure of reduced wild-type ArsC with Cys-10 in the center of the image. The P-loop is fully structured, despite the absence of bound oxyanion (2.0 Å). (C) In the structure of C15A ArsC-HAsO[ - ], an arsenic is covalently bound on Cys-10, surrounded by three oxygens in a plane and a water molecule opposite the sulfur of Cys-10 (1.4 Å). (D) Oxidized ArsC C89L with the intermediate Cys-10-Cys-82 disulfide bond (1.6 Å). (E) A view on the flexible looped-out region of oxidized ArsC C89L, where Cys-89 has left the hydrophobic core and is replaced by Leu-92 upon Cys-10-Cys-82 formation. The electron density in this highly flexible region is not so well defined. (F) A view on the surface of oxidized ArsC C10SC15A (6) with the Cys-82-Cys-89 disulfide bond. 		Figure 4.
Fig. 4. The movement of the "conformational switch" in the flexible segment (residues 80-98) trapped in four different ArsC crystals. Starting with a helix in the reduced ArsC wild type (blue), via oxidized ArsC C89L (Cys-10-Cys-82) in the first (yellow) and in the second (red) molecule in the asymmetric unit to finally looping out to form the C82-C89 disulfide (green). The two arrows indicate the movement of L92 and C89.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20960080 C.Yu, B.Xia, and C.Jin (2011).
(1)H, (13)C and (15)N resonance assignments of the arsenate reductase from Synechocystis sp. strain PCC 6803.
  Biomol NMR Assign, 5, 85-87.
PDB codes: 2l17 2l18 2l19
21258851 S.Jain, B.Saluja, A.Gupta, S.S.Marla, and R.Goel (2011).
Validation of Arsenic Resistance in Bacillus cereus Strain AG27 by Comparative Protein Modeling of arsC Gene Product.
  Protein J, 30, 91.  
20625793 E.Pedone, D.Limauro, K.D'Ambrosio, G.De Simone, and S.Bartolucci (2010).
Multiple catalytically active thioredoxin folds: a winning strategy for many functions.
  Cell Mol Life Sci, 67, 3797-3814.  
19634988 M.A.Wouters, S.W.Fan, and N.L.Haworth (2010).
Disulfides as redox switches: from molecular mechanisms to functional significance.
  Antioxid Redox Signal, 12, 53-91.  
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.  
19304854 L.López-Maury, A.M.Sánchez-Riego, J.C.Reyes, and F.J.Florencio (2009).
The glutathione/glutaredoxin system is essential for arsenate reduction in Synechocystis sp. strain PCC 6803.
  J Bacteriol, 191, 3534-3543.  
19424433 S.M.Marino, and V.N.Gladyshev (2009).
A structure-based approach for detection of thiol oxidoreductases and their catalytic redox-active cysteine residues.
  PLoS Comput Biol, 5, e1000383.  
19598234 S.W.Fan, R.A.George, N.L.Haworth, L.L.Feng, J.Y.Liu, and M.A.Wouters (2009).
Conformational changes in redox pairs of protein structures.
  Protein Sci, 18, 1745-1765.  
17609383 D.S.Touw, C.E.Nordman, J.A.Stuckey, and V.L.Pecoraro (2007).
Identifying important structural characteristics of arsenic resistance proteins by using designed three-stranded coiled coils.
  Proc Natl Acad Sci U S A, 104, 11969-11974.
PDB code: 2jgo
16570626 G.De la Rosa, J.G.Parsons, A.Martinez-Martinez, J.R.Peralta-Videa, and J.L.Gardea-Torresdey (2006).
Spectroscopic study of the impact of arsenic speciation on arsenic/phosphorus uptake and plant growth in tumbleweed (Salsola kali).
  Environ Sci Technol, 40, 1991-1996.  
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.  
15890001 A.Salmeen, and D.Barford (2005).
Functions and mechanisms of redox regulation of cysteine-based phosphatases.
  Antioxid Redox Signal, 7, 560-577.  
16332858 F.S.Islam, R.L.Pederick, A.G.Gault, L.K.Adams, D.A.Polya, J.M.Charnock, and J.R.Lloyd (2005).
Interactions between the Fe(III)-reducing bacterium Geobacter sulfurreducens and arsenate, and capture of the metalloid by biogenic Fe(II).
  Appl Environ Microbiol, 71, 8642-8648.  
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.  
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
12618461 L.I.Leichert, C.Scharf, and M.Hecker (2003).
Global characterization of disulfide stress in Bacillus subtilis.
  J Bacteriol, 185, 1967-1975.  
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.  
12777806 P.Retailleau, and T.Prangé (2003).
Phasing power at the K absorption edge of organic arsenic.
  Acta Crystallogr D Biol Crystallogr, 59, 887-896.
PDB code: 1n4f
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.  
12829274 S.Silver (2003).
Bacterial silver resistance: molecular biology and uses and misuses of silver compounds.
  FEMS Microbiol Rev, 27, 341-353.  
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.

 

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