Protein Science, Vol 3, Issue 5 799-809, Copyright © 1994 by Cold Spring Harbor Laboratory Press

ARTICLE

Structure of glutathione reductase from Escherichia coli at 1.86 A resolution: Comparison with the enzyme from human erythrocytes

PRE. MITTL and G. E. SCHULZ
Institut fur Organische Chemie und Biochemie, Albert-Ludwigs-Universitat, 79104 Freiburg im Breisgau, Germany

The crystal structure of the dimeric flavoenzyme glutathione reductase from Escherichia coli was determined and refined to an R-factor of 16.8% at 1.86 A resolution. The molecular 2-fold axis of the dimer is local but very close to a possible crystallographic 2-fold axis; the slight asymmetry could be rationalized from the packing contacts. The 2 crystallographically independent subunits of the dimer are virtually identical, yielding no structural clue on possible cooperativity. The structure was compared with the well-known structure of the homologous enzyme from human erythrocytes with 52% sequence identity. Significant differences were found at the dimer interface, where the human enzyme has a disulfide bridge, whereas the E. coli enzyme has an antiparallel {beta}-sheet connecting the subunits. The differences at the glutathione binding site and in particular a deformation caused by a LeuIle exchange indicate why the E. coli enzyme accepts trypanothione much better than the human enzyme. The reported structure provides a frame for explaining numerous published engineering results in detail and for guiding further ones.
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