Crystal structure of activated ModE reveals conformational changes involving both oxyanion and DNA-binding domains

TY - JOUR

T1 - Crystal structure of activated ModE reveals conformational changes involving both oxyanion and DNA-binding domains

AU - Schuttelkopf, Alexander W.

AU - Boxer, David H.

AU - Hunter, William N.

N1 - dc.publisher: Elsevier

PY - 2003

Y1 - 2003

N2 - ModE is a bacterial transcriptional regulator that orchestrates many aspects of molybdenum metabolism by binding to specific DNA sequences in a molybdate-dependent fashion. We present the crystal structure of Escherichia coli ModE in complex with molybdate, which was determined at 2.75 Å from a merohedrally twinned crystal (twin fraction˜0.30) with space group P43. We now have structures of ModE in both its “switched on” (ligand-bound) and “switched off” (apo) states. Comparison with the apo structure shows that ligand binding leads to extensive conformational changes not only in the molybdate-binding domain, but also in the DNA-binding domain. The most obvious difference is the loss of the pronounced asymmetry between the two chains of the ModE dimer, which had been a characteristic property of the apo structure. Another major change concerns the relative orientation of the two DNA-interacting winged helix-turn-helix motifs. Manual docking of an idealized DNA structure suggests that this conformational change should improve DNA binding of the activated molybdate-bound ModE.

AB - ModE is a bacterial transcriptional regulator that orchestrates many aspects of molybdenum metabolism by binding to specific DNA sequences in a molybdate-dependent fashion. We present the crystal structure of Escherichia coli ModE in complex with molybdate, which was determined at 2.75 Å from a merohedrally twinned crystal (twin fraction˜0.30) with space group P43. We now have structures of ModE in both its “switched on” (ligand-bound) and “switched off” (apo) states. Comparison with the apo structure shows that ligand binding leads to extensive conformational changes not only in the molybdate-binding domain, but also in the DNA-binding domain. The most obvious difference is the loss of the pronounced asymmetry between the two chains of the ModE dimer, which had been a characteristic property of the apo structure. Another major change concerns the relative orientation of the two DNA-interacting winged helix-turn-helix motifs. Manual docking of an idealized DNA structure suggests that this conformational change should improve DNA binding of the activated molybdate-bound ModE.

U2 - 10.1016/S0022-2836(02)01358-X

DO - 10.1016/S0022-2836(02)01358-X

M3 - Article

SN - 0022-2836

VL - 326

SP - 761

EP - 767

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

IS - 3

ER -