Zinc(II)-mediated inhibition of a ribonuclease by an N-hydroxyurea nucleotide.
The inhibition of ribonuclease Bi by 3'-N-hydroxyurea-3'-deoxythymidine 5'-phosphate is enhanced by 30-fold in the presence of Zn(2+). Thus, an N-hydroxyurea nucleotide can recruit Zn(2+) to inhibit the enzymatic activity of a ribonuclease. This result engenders a general strategy for the inhibition of non-metalloenzymes by metal complexes.
Higgin
Joshua J
JJ
Department of Chemistry, University of Wisconsin-Madison, Madfison, WI 53706, USA.
Yakovlev
Gennady I
GI
Mitkevich
Vladimir A
VA
Makarov
Alexander A
AA
Raines
Ronald T
RT
D004722:Endoribonucleases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006918:Hydroxyurea / Q000494:pharmacology*; D007700:Kinetics; D012260:Ribonucleases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D015032:Zinc / Q000494:pharmacology*
C476322:3'-N-hydroxyurea-3'-deoxythymidine 5'-phosphate; D004791:Enzyme Inhibitors; D004722:Endoribonucleases; D012260:Ribonucleases; C022543:ribonuclease T(2); D015032:Zinc; D013936:Thymidine; D006918:Hydroxyurea