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PDBsum entry 1fw1

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Isomerase/transferase PDB id
1fw1
Jmol
Contents
Protein chain
208 a.a. *
Ligands
SO4
DTT
GSH
Waters ×109
* Residue conservation analysis
PDB id:
1fw1
Name: Isomerase/transferase
Title: Glutathione transferase zeta/maleylacetoacetate isomerase
Structure: Glutathione transferase zeta. Chain: a. Synonym: maleylacetoacetate isomerase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
Resolution:
1.90Å     R-factor:   0.234     R-free:   0.281
Authors: G.Polekhina,P.G.Board,A.C.Blackburn,M.W.Parker
Key ref:
G.Polekhina et al. (2001). Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity. Biochemistry, 40, 1567-1576. PubMed id: 11327815 DOI: 10.1021/bi002249z
Date:
20-Sep-00     Release date:   26-Sep-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O43708  (MAAI_HUMAN) -  Maleylacetoacetate isomerase
Seq:
Struc:
216 a.a.
208 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 2: E.C.2.5.1.18  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
RX
+
glutathione
Bound ligand (Het Group name = GSH)
corresponds exactly
= HX
+ R-S-glutathione
   Enzyme class 3: E.C.5.2.1.2  - Maleylacetoacetate isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 4-maleylacetoacetate = 4-fumarylacetoacetate
4-maleylacetoacetate
= 4-fumarylacetoacetate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   3 terms 
  Biological process     metabolic process   10 terms 
  Biochemical function     catalytic activity     8 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi002249z Biochemistry 40:1567-1576 (2001)
PubMed id: 11327815  
 
 
Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity.
G.Polekhina, P.G.Board, A.C.Blackburn, M.W.Parker.
 
  ABSTRACT  
 
Maleylacetoacetate isomerase (MAAI), a key enzyme in the metabolic degradation of phenylalanine and tyrosine, catalyzes the glutathione-dependent isomerization of maleylacetoacetate to fumarylacetoacetate. Deficiencies in enzymes along the degradation pathway lead to serious diseases including phenylketonuria, alkaptonuria, and the fatal disease, hereditary tyrosinemia type I. The structure of MAAI might prove useful in the design of inhibitors that could be used in the clinical management of the latter disease. Here we report the crystal structure of human MAAI at 1.9 A resolution in complex with glutathione and a sulfate ion which mimics substrate binding. The enzyme has previously been shown to belong to the zeta class of the glutathione S-transferase (GST) superfamily based on limited sequence similarity. The structure of MAAI shows that it does adopt the GST canonical fold but with a number of functionally important differences. The structure provides insights into the molecular bases of the remarkable array of different reactions the enzyme is capable of performing including isomerization, oxygenation, dehalogenation, peroxidation, and transferase activity.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21428697 A.Oakley (2011).
Glutathione transferases: a structural perspective.
  Drug Metab Rev, 43, 138-151.  
  21303221 P.G.Board, and M.W.Anders (2011).
Glutathione transferase zeta: discovery, polymorphic variants, catalysis, inactivation, and properties of Gstz1-/- mice.
  Drug Metab Rev, 43, 215-225.  
20622445 D.Chen, J.Liu, J.Liu, and X.Chen (2010).
Evolution of the catalytic activity of Arabidopsis thaliana glutathione transferase zeta class-1 by saturation mutagenesis.
  Biosci Biotechnol Biochem, 74, 1458-1461.  
20843339 R.R.da Fonseca, W.E.Johnson, S.J.O'Brien, V.Vasconcelos, and A.Antunes (2010).
Molecular evolution and the role of oxidative stress in the expansion and functional diversification of cytosolic glutathione transferases.
  BMC Evol Biol, 10, 281.  
20331431 X.Chen, J.Liu, P.Yang, and D.Chen (2010).
Identifying functional residues in arabidopsis thaliana zeta class glutathione S-transferase through screening inactive point mutants.
  Biochemistry (Mosc), 75, 110-120.  
18373941 K.Zheng, P.G.Board, X.Fei, Y.Sun, S.Lv, G.Yan, J.Liu, J.Shen, and G.Luo (2008).
A novel selenium-containing glutathione transferase zeta1-1, the activity of which surpasses the level of some native glutathione peroxidases.
  Int J Biochem Cell Biol, 40, 2090-2097.  
17682821 B.Blanchette, X.Feng, and B.R.Singh (2007).
Marine glutathione S-transferases.
  Mar Biotechnol (NY), 9, 513-542.  
17428791 R.Wang, Y.J.Yin, F.Wang, M.Li, J.Feng, H.M.Zhang, J.P.Zhang, S.J.Liu, and W.R.Chang (2007).
Crystal structures and site-directed mutagenesis of a mycothiol-dependent enzyme reveal a novel folding and molecular basis for mycothiol-mediated maleylpyruvate isomerization.
  J Biol Chem, 282, 16288-16294.
PDB codes: 2nsf 2nsg
16189827 D.J.Schuller, Q.Liu, I.A.Kriksunov, A.M.Campbell, J.Barrett, P.M.Brophy, and Q.Hao (2005).
Crystal structure of a new class of glutathione transferase from the model human hookworm nematode Heligmosomoides polygyrus.
  Proteins, 61, 1024-1031.
PDB code: 1tw9
16195232 E.Cesareo, L.J.Parker, J.Z.Pedersen, M.Nuccetelli, A.P.Mazzetti, A.Pastore, G.Federici, A.M.Caccuri, G.Ricci, J.J.Adams, M.W.Parker, and M.Lo Bello (2005).
Nitrosylation of human glutathione transferase P1-1 with dinitrosyl diglutathionyl iron complex in vitro and in vivo.
  J Biol Chem, 280, 42172-42180.
PDB code: 1zgn
16081649 J.Li, Z.Xia, and J.Ding (2005).
Thioredoxin-like domain of human kappa class glutathione transferase reveals sequence homology and structure similarity to the theta class enzyme.
  Protein Sci, 14, 2361-2369.
PDB code: 1yzx
15173170 G.Ricci, P.Turella, F.De Maria, G.Antonini, L.Nardocci, P.G.Board, M.W.Parker, M.G.Carbonelli, G.Federici, and A.M.Caccuri (2004).
Binding and kinetic mechanisms of the Zeta class glutathione transferase.
  J Biol Chem, 279, 33336-33342.  
12587874 F.L.Theodoulou, I.M.Clark, X.L.He, K.E.Pallett, D.J.Cole, and D.L.Hallahan (2003).
Co-induction of glutathione-S-transferases and multidrug resistance associated protein by xenobiotics in wheat.
  Pest Manag Sci, 59, 202-214.  
12972429 M.G.Jeppesen, P.Ortiz, W.Shepard, T.G.Kinzy, J.Nyborg, and G.R.Andersen (2003).
The crystal structure of the glutathione S-transferase-like domain of elongation factor 1Bgamma from Saccharomyces cerevisiae.
  J Biol Chem, 278, 47190-47198.
PDB code: 1nhy
12052898 J.M.Fernández-Cañón, M.W.Baetscher, M.Finegold, T.Burlingame, K.M.Gibson, and M.Grompe (2002).
Maleylacetoacetate isomerase (MAAI/GSTZ)-deficient mice reveal a glutathione-dependent nonenzymatic bypass in tyrosine catabolism.
  Mol Cell Biol, 22, 4943-4951.  
11692075 A.C.Blackburn, M.Coggan, H.F.Tzeng, H.Lantum, G.Polekhina, M.W.Parker, M.W.Anders, and P.G.Board (2001).
GSTZ1d: a new allele of glutathione transferase zeta and maleylacetoacetate isomerase.
  Pharmacogenetics, 11, 671-678.  
11453994 D.Gisi, J.Maillard, J.U.Flanagan, J.Rossjohn, G.Chelvanayagam, P.G.Board, M.W.Parker, T.Leisinger, and S.Vuilleumier (2001).
Dichloromethane mediated in vivo selection and functional characterization of rat glutathione S-transferase theta 1-1 variants.
  Eur J Biochem, 268, 4001-4010.  
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.