Crystal structure of an archaeal Rad51 homologue in complex with a metatungstate inhibitor.
Archaeal RadAs are close homologues of eukaryal Rad51s ( approximately 40% sequence identities). These recombinases promote a hallmark strand exchange process between homologous single-stranded and double-stranded DNA substrates. This DNA-repairing function also plays a key role in cancer cells' resistance to chemo- and radiotherapy. Inhibition of the strand exchange process may render cancer cells more susceptible to therapeutic treatment. We found that metatungstate is a potent inhibitor of RadA from Methanococcus voltae. The tungsten cluster binds RadA in the axial DNA-binding groove. This polyanionic species appears to inhibit RadA by locking the protein in its inactive conformation.
Li
Yang
Y
Department of Biochemistry, University of Saskatchewan, A3 Health Sciences Building, 107 Wiggins Road, Saskatoon, Saskatchewan, Canada S7N 5E5.
He
Yujiong
Y
Luo
Yu
Y
D000255:Adenosine Triphosphate / Q000737:chemistry; D001483:Base Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D017931:DNA Primers; D006868:Hydrolysis; D017017:Methanococcus / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D051135:Rad51 Recombinase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D017973:Tungsten Compounds / Q000737:chemistry*
D017931:DNA Primers; D017973:Tungsten Compounds; D000255:Adenosine Triphosphate; D004247:DNA; D051135:Rad51 Recombinase; C045951:tungstate