C. Ban et W. Yang, CRYSTAL-STRUCTURE AND ATPASE ACTIVITY OF MUTL - IMPLICATIONS FOR DNA-REPAIR AND MUTAGENESIS, Cell (Cambridge), 95(4), 1998, pp. 541-552
MutL and its homologs are essential for DNA mismatch repair. Mutations
in genes encoding human homologs of MutL cause multiorgan cancer susc
eptibility. We have determined the crystal structure of a 40 kDa N-ter
minal fragment of E. coli MutL that retains all of the conserved resid
ues in the MutL family. The structure of MutL is homologous to that of
an ATPase-containing fragment of DNA gyrase. We have demonstrated tha
t MutL binds and hydrolyzes ATP to ADP and Pi. Mutations in the MutL f
amily that cause deficiencies in DNA mismatch repair and a predisposit
ion to cancer mainly occur in the putative ATP-binding site. We provid
e evidence that the flexible, yet conserved, loops surrounding this AT
P-binding site undergo conformational changes upon ATP hydrolysis ther
eby modulating interactions between MutL and other components of the r
epair machinery.