C. Ban et W. Yang, STRUCTURAL BASIS FOR MUTH ACTIVATION IN ESCHERICHIA-COLI MISMATCH REPAIR AND RELATIONSHIP OF MUTH TO RESTRICTION ENDONUCLEASES, EMBO journal, 17(5), 1998, pp. 1526-1534
MutS, MutL and MutH are the three essential proteins for initiation of
methyl-directed DNA mismatch repair to correct mistakes made during D
NA replication in Escherichia coli, MutH cleaves a newly synthesized a
nd unmethylated daughter strand 5' to the sequence d(GATC) in a hemi-m
ethylated duplex, Activation of MutH requires the recognition of a DNA
mismatch by MutS and MutL. We have crystallized MutH in two space gro
ups and solved the structures at 1.7 and 2.3 Angstrom resolution, resp
ectively, The active site of MutH is located at an interface between t
wo subdomains that pivot relative to one another, as revealed by compa
rison of the crystal structures, and this presumably regulates the nuc
lease activity, The relative motion of the two subdomains in MutH corr
elates with the position of a protruding C-terminal helix, This helix
appears to act. as a molecular lever through which MutS and MutL may c
ommunicate the detection of a DNA mismatch and activate MutH, With seq
uence homology to Sau3AI and structural similarity to PvuII endonuclea
se, MutH is clearly related to these enzymes by divergent evolution, a
nd this suggests that type II restriction endonucleases evolved from a
common ancestor.