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PDBsum entry 2h8a

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protein ligands links
Transferase PDB id
2h8a
Jmol
Contents
Protein chain
121 a.a. *
Ligands
GSH
* Residue conservation analysis
PDB id:
2h8a
Name: Transferase
Title: Structure of microsomal glutathione transferase 1 in complex glutathione
Structure: Microsomal glutathione s-transferase 1. Chain: a. Synonym: microsomal gst- 1, microsomal gst-i. Ec: 2.5.1.18
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116
Authors: H.Hebert
Key ref:
P.J.Holm et al. (2006). Structural basis for detoxification and oxidative stress protection in membranes. J Mol Biol, 360, 934-945. PubMed id: 16806268 DOI: 10.1016/j.jmb.2006.05.056
Date:
07-Jun-06     Release date:   22-May-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08011  (MGST1_RAT) -  Microsomal glutathione S-transferase 1
Seq:
Struc:
155 a.a.
121 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: 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
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   11 terms 
  Biological process     cellular response to lipid hydroperoxide   8 terms 
  Biochemical function     transferase activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2006.05.056 J Mol Biol 360:934-945 (2006)
PubMed id: 16806268  
 
 
Structural basis for detoxification and oxidative stress protection in membranes.
P.J.Holm, P.Bhakat, C.Jegerschöld, N.Gyobu, K.Mitsuoka, Y.Fujiyoshi, R.Morgenstern, H.Hebert.
 
  ABSTRACT  
 
Synthesis of mediators of fever, pain and inflammation as well as protection against reactive molecules and oxidative stress is a hallmark of the MAPEG superfamily (membrane associated proteins in eicosanoid and glutathione metabolism). The structure of a MAPEG member, rat microsomal glutathione transferase 1, at 3.2 A resolution, solved here in complex with glutathione by electron crystallography, defines the active site location and a cytosolic domain involved in enzyme activation. The glutathione binding site is found to be different from that of the canonical soluble glutathione transferases. The architecture of the homotrimer supports a catalytic mechanism involving subunit interactions and reveals both cytosolic and membraneous substrate entry sites, providing a rationale for the membrane location of the enzyme.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Close contacts of MGST1 trimers. In both the p6 ((a) and (b)) and the p22[1]2[1] ((c) and (d)) 2D crystals the closest approach of MGST trimers is found between the symmetric tyrosine pairs Y115-Y145 and Y145-Y115, respectively.
Figure 7.
Figure 7. Catalytic mechanism involving three bound GSH molecules to the MGST1 homotrimer. The locations of the substrates relatively to the innermost TM2 helices of the enzyme form an annular interaction network. This provides a structural basis for one-third of the sites reactivity through tight binding simultaneously of only one GSH in the catalytically competent thiolate form. In addition, the on/off rate of thiolate formation, possibly modulated by the close proximity to the extension of TM1, the proline-rich loop between TM3 and TM4 and domain E, may determine the dynamics of the active site.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 360, 934-945) copyright 2006.  
  Figures were selected by an automated process.  

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.  
20561794 H.Wang, and K.H.Downing (2011).
Specimen preparation for electron diffraction of thin crystals.
  Micron, 42, 132-140.  
20938980 K.Illergård, A.Kauko, and A.Elofsson (2011).
Why are polar residues within the membrane core evolutionary conserved?
  Proteins, 79, 79-91.  
21495795 R.Morgenstern, J.Zhang, and K.Johansson (2011).
Microsomal glutathione transferase 1: mechanism and functional roles.
  Drug Metab Rev, 43, 300-306.  
21428695 Y.Aniya, and N.Imaizumi (2011).
Mitochondrial glutathione transferases involving a new function for membrane permeability transition pore regulation.
  Drug Metab Rev, 43, 292-299.  
20369883 A.Hamza, M.Tong, M.D.AbdulHameed, J.Liu, A.C.Goren, H.H.Tai, and C.G.Zhan (2010).
Understanding microscopic binding of human microsomal prostaglandin E synthase-1 (mPGES-1) trimer with substrate PGH2 and cofactor GSH: insights from computational alanine scanning and site-directed mutagenesis.
  J Phys Chem B, 114, 5605-5616.  
20980252 A.Rinaldo-Matthis, A.Wetterholm, D.Martinez Molina, J.Holm, D.Niegowski, E.Ohlson, P.Nordlund, R.Morgenstern, and J.Z.Haeggström (2010).
Arginine 104 is a key catalytic residue in leukotriene C4 synthase.
  J Biol Chem, 285, 40771-40776.
PDB code: 3leo
20349145 C.Kim, M.Vink, M.Hu, J.Love, D.L.Stokes, and I.Ubarretxena-Belandia (2010).
An automated pipeline to screen membrane protein 2D crystallization.
  J Struct Funct Genomics, 11, 155-166.  
19826804 K.McLuskey, A.W.Roszak, Y.Zhu, and N.W.Isaacs (2010).
Crystal structures of all-alpha type membrane proteins.
  Eur Biophys J, 39, 723-755.  
20667175 K.R.Vinothkumar, and R.Henderson (2010).
Structures of membrane proteins.
  Q Rev Biophys, 43, 65.  
20399185 M.F.Rosenberg, Z.Bikadi, J.Chan, X.Liu, Z.Ni, X.Cai, R.C.Ford, and Q.Mao (2010).
The human breast cancer resistance protein (BCRP/ABCG2) shows conformational changes with mitoxantrone.
  Structure, 18, 482-493.  
20739006 M.Miyano, H.Ago, H.Saino, T.Hori, and K.Ida (2010).
Internally bridging water molecule in transmembrane alpha-helical kink.
  Curr Opin Struct Biol, 20, 456-463.  
20605783 S.C.Pawelzik, N.R.Uda, L.Spahiu, C.Jegerschöld, P.Stenberg, H.Hebert, R.Morgenstern, and P.J.Jakobsson (2010).
Identification of key residues determining species differences in inhibitor binding of microsomal prostaglandin E synthase-1.
  J Biol Chem, 285, 29254-29261.  
20410586 S.Nakama, N.Oshiro, and Y.Aniya (2010).
Activation of rat liver microsomal glutathione transferase by hepsin.
  Biol Pharm Bull, 33, 561-567.  
19416719 J.Alander, J.Lengqvist, P.J.Holm, R.Svensson, P.Gerbaux, R.H.Heuvel, H.Hebert, W.J.Griffiths, R.N.Armstrong, and R.Morgenstern (2009).
Microsomal glutathione transferase 1 exhibits one-third-of-the-sites-reactivity towards glutathione.
  Arch Biochem Biophys, 487, 42-48.  
18777160 L.Xing, R.G.Kurumbail, R.B.Frazier, M.S.Davies, H.Fujiwara, R.A.Weinberg, J.K.Gierse, N.Caspers, J.S.Carter, J.J.McDonald, W.M.Moore, and M.L.Vazquez (2009).
Homo-timeric structural model of human microsomal prostaglandin E synthase-1 and characterization of its substrate/inhibitor binding interactions.
  J Comput Aided Mol Des, 23, 13-24.  
19564688 N.Volkmann (2009).
Confidence intervals for fitting of atomic models into low-resolution densities.
  Acta Crystallogr D Biol Crystallogr, 65, 679-689.  
18984580 T.Hammarberg, M.Hamberg, A.Wetterholm, H.Hansson, B.Samuelsson, and J.Z.Haeggström (2009).
Mutation of a Critical Arginine in Microsomal Prostaglandin E Synthase-1 Shifts the Isomerase Activity to a Reductase Activity That Converts Prostaglandin H2 into Prostaglandin F2{alpha}.
  J Biol Chem, 284, 301-305.  
18682561 C.Jegerschöld, S.C.Pawelzik, P.Purhonen, P.Bhakat, K.R.Gheorghe, N.Gyobu, K.Mitsuoka, R.Morgenstern, P.J.Jakobsson, and H.Hebert (2008).
Structural basis for induced formation of the inflammatory mediator prostaglandin E2.
  Proc Natl Acad Sci U S A, 105, 11110-11115.
PDB code: 3dww
18621661 F.Forneris, and A.Mattevi (2008).
Enzymes without borders: mobilizing substrates, delivering products.
  Science, 321, 213-216.  
18755273 Y.Fujiyoshi, and N.Unwin (2008).
Electron crystallography of proteins in membranes.
  Curr Opin Struct Biol, 18, 587-592.  
17600184 A.D.Ferguson, B.M.McKeever, S.Xu, D.Wisniewski, D.K.Miller, T.T.Yamin, R.H.Spencer, L.Chu, F.Ujjainwalla, B.R.Cunningham, J.F.Evans, and J.W.Becker (2007).
Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein.
  Science, 317, 510-512.
PDB codes: 2q7m 2q7r
17632546 D.Martinez Molina, A.Wetterholm, A.Kohl, A.A.McCarthy, D.Niegowski, E.Ohlson, T.Hammarberg, S.Eshaghi, J.Z.Haeggström, and P.Nordlund (2007).
Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase.
  Nature, 448, 613-616.
PDB codes: 2uuh 2uui
17632548 H.Ago, Y.Kanaoka, D.Irikura, B.K.Lam, T.Shimamura, K.F.Austen, and M.Miyano (2007).
Crystal structure of a human membrane protein involved in cysteinyl leukotriene biosynthesis.
  Nature, 448, 609-612.
PDB code: 2pno
17638580 J.E.Norville, D.F.Kelly, T.F.Knight, A.M.Belcher, and T.Walz (2007).
7A projection map of the S-layer protein sbpA obtained with trehalose-embedded monolayer crystals.
  J Struct Biol, 160, 313-323.  
17951070 M.Vink, K.Derr, J.Love, D.L.Stokes, and I.Ubarretxena-Belandia (2007).
A high-throughput strategy to screen 2D crystallization trials of membrane proteins.
  J Struct Biol, 160, 295-304.  
17723294 R.K.Hite, S.Raunser, and T.Walz (2007).
Revival of electron crystallography.
  Curr Opin Struct Biol, 17, 389-395.  
17904383 X.Zeng, B.Gipson, Z.Y.Zheng, L.Renault, and H.Stahlberg (2007).
Automatic lattice determination for two-dimensional crystal images.
  J Struct Biol, 160, 353-361.  
17103018 L.Renault, H.T.Chou, P.L.Chiu, R.M.Hill, X.Zeng, B.Gipson, Z.Y.Zhang, A.Cheng, V.Unger, and H.Stahlberg (2006).
Milestones in electron crystallography.
  J Comput Aided Mol Des, 20, 519-527.  
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.