PDBsum entry 1flj

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Lyase PDB id
Protein chain
260 a.a. *
GSH ×2
Waters ×216
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Crystal structure of s-glutathiolated carbonic anhydrase iii
Structure: Carbonic anhydrase iii. Chain: a. Synonym: carbonate dehydratase iii, ca-iii. Ec:
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: liver
1.80Å     R-factor:   0.155     R-free:   0.213
Authors: R.J.Mallis,B.W.Poland,T.K.Chatterjee,R.A.Fisher,S.Darmawan, R.B.Honzatko,J.A.Thomas
Key ref:
R.J.Mallis et al. (2000). Crystal structure of S-glutathiolated carbonic anhydrase III. FEBS Lett, 482, 237-241. PubMed id: 11024467 DOI: 10.1016/S0014-5793(00)02022-6
14-Aug-00     Release date:   04-Sep-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P14141  (CAH3_RAT) -  Carbonic anhydrase 3
260 a.a.
259 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Carbonate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: H2CO3 = CO2 + H2O
= CO(2)
+ H(2)O
      Cofactor: Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     one-carbon metabolic process   3 terms 
  Biochemical function     lyase activity     5 terms  


    Added reference    
DOI no: 10.1016/S0014-5793(00)02022-6 FEBS Lett 482:237-241 (2000)
PubMed id: 11024467  
Crystal structure of S-glutathiolated carbonic anhydrase III.
R.J.Mallis, B.W.Poland, T.K.Chatterjee, R.A.Fisher, S.Darmawan, R.B.Honzatko, J.A.Thomas.
S-Glutathiolation of carbonic anhydrase III (CAIII) occurs rapidly in hepatocytes under oxidative stress. The crystal structure of the S-glutathiolated CAIII from rat liver reveals covalent adducts on cysteines 183 and 188. Electrostatic charge and steric contacts at each modification site inversely correlate with the relative rates of reactivity of these cysteines toward glutathione (GSH). Diffuse electron density associated with the GSH adducts suggests a lack of preferred bonding interactions between CAIII and the glutathionyl moieties. Hence, the GSH adducts are available for binding by a protein capable of reducing this mixed disulfide. These properties are consistent with the participation of CAIII in the protection/recovery from the damaging effects of oxidative agents.
  Selected figure(s)  
Figure 4.
Fig. 4. Stereo, surface representation of S-glutathiolated CAIII in the vicinity of the Cys183 adduct. The two conformers of the Cys183 adduct are represented by wireframe models. The disulfide bonds between GSH1 and Cys183 are shown as thin black lines. The view is approximately the same as that in Fig. 3B. The image was generated using MolMol [28]. A: Conformation 1 of the Cys183–GSH1 adduct. This is the same conformation of Cys183 as is found in the reduced bovine CAIII structure [27]. B: Conformation 2 of Cys183–GSH1 adduct.
Figure 5.
Fig. 5. Electrostatic and solvent-accessible surface representation of CAIII in stereo. Dark gray coloration represents a positive charge, light gray a negative charge and white a neutral charge. The position of S^γ of the GSH adducts are indicated by white balls. The lower portion of the figure shows the electrostatic surface of CAIII when the cysteines are in conformation 1. This is the same conformation as that of the reduced bovine CAIII model [21]. The upper portion of the figure shows the surface when Cys183 is in conformation 2. The electrostatic and surface calculations were carried out using MolMol [28], which utilizes the algorithm of Nicholls and Honig [29].
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS Lett (2000, 482, 237-241) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18092936 I.Dalle-Donne, A.Milzani, N.Gagliano, R.Colombo, D.Giustarini, and R.Rossi (2008).
Molecular mechanisms and potential clinical significance of S-glutathionylation.
  Antioxid Redox Signal, 10, 445-473.  
18335973 V.M.Krishnamurthy, G.K.Kaufman, A.R.Urbach, I.Gitlin, K.L.Gudiksen, D.B.Weibel, and G.M.Whitesides (2008).
Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding.
  Chem Rev, 108, 946.  
18395187 Z.Huang, J.T.Pinto, H.Deng, and J.P.Richie (2008).
Inhibition of caspase-3 activity and activation by protein glutathionylation.
  Biochem Pharmacol, 75, 2234-2244.  
17510781 A.Rizzello, M.A.Ciardiello, R.Acierno, V.Carratore, T.Verri, G.di Prisco, C.Storelli, and M.Maffia (2007).
Biochemical characterization of a S-glutathionylated carbonic anhydrase isolated from gills of the Antarctic icefish Chionodraco hamatus.
  Protein J, 26, 335-348.  
17722187 A.Zinellu, S.Sotgia, A.M.Posadino, V.Pasciu, E.Zinellu, M.F.Usai, B.Scanu, R.Chessa, L.Gaspa, B.Tadolini, L.Deiana, and C.Carru (2007).
Protein-bound glutathione measurement in cultured cells by CZE with LIF detection.
  Electrophoresis, 28, 3277-3283.  
17407288 D.K.Srivastava, K.M.Jude, A.L.Banerjee, M.Haldar, S.Manokaran, J.Kooren, S.Mallik, and D.W.Christianson (2007).
Structural analysis of charge discrimination in the binding of inhibitors to human carbonic anhydrases I and II.
  J Am Chem Soc, 129, 5528-5537.
PDB codes: 2nmx 2nn1 2nn7 2nng 2nno 2nns 2nnv
17697933 I.Dalle-Donne, R.Rossi, D.Giustarini, R.Colombo, and A.Milzani (2007).
S-glutathionylation in protein redox regulation.
  Free Radic Biol Med, 43, 883-898.  
17427958 I.Elder, Z.Fisher, P.J.Laipis, C.Tu, R.McKenna, and D.N.Silverman (2007).
Structural and kinetic analysis of proton shuttle residues in the active site of human carbonic anhydrase III.
  Proteins, 68, 337-343.
PDB codes: 2hfw 2hfx 2hfy 3uyn 3uyq
17573429 S.Marino, K.Hayakawa, K.Hatada, M.Benfatto, A.Rizzello, M.Maffia, and L.Bubacco (2007).
Structural features that govern enzymatic activity in carbonic anhydrase from a low-temperature adapted fish, Chionodraco hamatus.
  Biophys J, 93, 2781-2790.  
16372262 P.Ghezzi, S.Casagrande, T.Massignan, M.Basso, E.Bellacchio, L.Mollica, E.Biasini, R.Tonelli, I.Eberini, E.Gianazza, W.W.Dai, M.Fratelli, M.Salmona, B.Sherry, and V.Bonetto (2006).
Redox regulation of cyclophilin A by glutathionylation.
  Proteomics, 6, 817-825.  
15998239 G.Kim, and R.L.Levine (2005).
Molecular determinants of S-glutathionylation of carbonic anhydrase 3.
  Antioxid Redox Signal, 7, 849-854.  
15998254 T.R.Hurd, N.J.Costa, C.C.Dahm, S.M.Beer, S.E.Brown, A.Filipovska, and M.P.Murphy (2005).
Glutathionylation of mitochondrial proteins.
  Antioxid Redox Signal, 7, 999.  
15031283 N.J.Cotton, B.Stoddard, and W.W.Parson (2004).
Oxidative inhibition of human soluble catechol-O-methyltransferase.
  J Biol Chem, 279, 23710-23718.  
15454425 S.Braun-Sand, M.Strajbl, and A.Warshel (2004).
Studies of proton translocations in biological systems: simulating proton transport in carbonic anhydrase by EVB-based models.
  Biophys J, 87, 2221-2239.  
15347644 S.M.Beer, E.R.Taylor, S.E.Brown, C.C.Dahm, N.J.Costa, M.J.Runswick, and M.P.Murphy (2004).
Glutaredoxin 2 catalyzes the reversible oxidation and glutathionylation of mitochondrial membrane thiol proteins: implications for mitochondrial redox regulation and antioxidant DEFENSE.
  J Biol Chem, 279, 47939-47951.  
  12930737 B.Knudsen, M.M.Miyamoto, P.J.Laipis, and D.N.Silverman (2003).
Using evolutionary rates to investigate protein functional divergence and conservation. A case study of the carbonic anhydrases.
  Genetics, 164, 1261-1269.  
12892645 M.F.Lou (2003).
Redox regulation in the lens.
  Prog Retin Eye Res, 22, 657-682.  
12171926 C.Tu, M.Qian, H.An, N.R.Wadhwa, D.Duda, C.Yoshioka, Y.Pathak, R.McKenna, P.J.Laipis, and D.N.Silverman (2002).
Kinetic analysis of multiple proton shuttles in the active site of human carbonic anhydrase.
  J Biol Chem, 277, 38870-38876.
PDB code: 1lzv
11976500 D.M.Duda, C.Yoshioka, L.Govindasamy, H.An, C.Tu, D.N.Silverman, and R.McKenna (2002).
Crystallization and preliminary X-ray analysis of human carbonic anhydrase III.
  Acta Crystallogr D Biol Crystallogr, 58, 849-852.  
11863462 H.An, C.Tu, D.Duda, I.Montanez-Clemente, K.Math, P.J.Laipis, R.McKenna, and D.N.Silverman (2002).
Chemical rescue in catalysis by human carbonic anhydrases II and III.
  Biochemistry, 41, 3235-3242.  
12033454 R.J.Mallis, M.J.Hamann, W.Zhao, T.Zhang, S.Hendrich, and J.A.Thomas (2002).
Irreversible thiol oxidation in carbonic anhydrase III: protection by S-glutathiolation and detection in aging rats.
  Biol Chem, 383, 649-662.  
12119401 S.Casagrande, V.Bonetto, M.Fratelli, E.Gianazza, I.Eberini, T.Massignan, M.Salmona, G.Chang, A.Holmgren, and P.Ghezzi (2002).
Glutathionylation of human thioredoxin: a possible crosstalk between the glutathione and thioredoxin systems.
  Proc Natl Acad Sci U S A, 99, 9745-9749.  
11493685 D.A.Whittington, A.Waheed, B.Ulmasov, G.N.Shah, J.H.Grubb, W.S.Sly, and D.W.Christianson (2001).
Crystal structure of the dimeric extracellular domain of human carbonic anhydrase XII, a bitopic membrane protein overexpressed in certain cancer tumor cells.
  Proc Natl Acad Sci U S A, 98, 9545-9550.
PDB codes: 1jcz 1jd0
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.