X-ray crystal structures of cytosolic glutathione S-transferases

Implications for protein architecture, substrate recognition and catalytic function

Authors

  • Heini DIRR,

    Corresponding author
    1. Department of Biochemistry, University of the Witwatersrand, Johannesburg, South Africa
    2. Max-Planck-Institut für Biochemie, Martinsried, Germany
      Correspondence to H. Dirr, Department of Biochemistry, University of the Witwatersrand, PO Wits, Johannesburg, South Africa 2050
      Fax: +11 403 1733.
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  • Peter REINEMER,

    1. Max-Planck-Institut für Biochemie, Martinsried, Germany
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  • Robert HUBER

    1. Max-Planck-Institut für Biochemie, Martinsried, Germany
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Correspondence to H. Dirr, Department of Biochemistry, University of the Witwatersrand, PO Wits, Johannesburg, South Africa 2050
Fax: +11 403 1733.

Abstract

Crystal structures of cytosolic glutathione S-transferases (EC 2.5.1.18), complexed with glutathione or its analogues, are reviewed. The atomic models define protein architectural relationships between the different gene classes in the superfamily, and reveal the molecular basis for substrate binding at the two adjacent subsites of the active site. Considerable progress has been made in understanding the mechanism whereby the thiol group of glutathione is destabilized (lowering its pKa) at the active site, a rate-enhancement strategy shared by the soluble glutathione S-transferases.

Abbreviations
GST

glutathione S-transferase

pGSTP1-1

hGSTA1-1, rGSTM1-1 etc., acronyms for the glutathione S-transferases (GST), the prefix indicating the species (p, porcine

h

human

r

rat

b

bovine

m

mouse

rb

rabbit

c

chicken

gp

guinea pig) while P, A, and M indicate gene class pi, alpha and mu, respectively; 1-1 indicates a dimer of two type-1 subunits

GSH

reduced glutathione

P1

P2 etc. and G1, G2 etc., designate peptide functional groups in glutathione and the corresponding G-site ligands of the glutathione S-transferases, respectively

G-site

glutathione-binding site

H-site

hydrophobic electrophile-binding site

Enzyme
 

Glutathione S-transferase (EC 2.5.1.18)

Ancillary

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