Inhibition of thermolysin and human alpha-thrombin by cobalt(III) Schiff base complexes.
Cobalt(III) Schiff base complexes have been shown to inhibit the replication of the ocular herpes virus. It is well known that these complexes have a high affinity for nitrogenous donors such as histidine residues, and it is possible that they bind to (and inhibit) an enzyme that is crucial to viral replication. In model studies, we have found that [Co(acacen)(NH3)2]+ is an effective irreversible inhibitor of thermolysin at millimolar concentrations; it also inhibits human alpha-thrombin. Axial ligand exchange with an active-site histidine is the proposed mechanism of inhibition. The activity of thermolysin and thrombin can be protected by binding a reversible inhibitor to the active site before addition of the cobalt(III) complex.
Division of Biology and the Beckman Institute, California Institute of Technology, Pasadena 91125, USA.
T
T
Takeuchi
A
A
Böttcher
C M
CM
Quezada
T J
TJ
Meade
H B
HB
Gray
D001665:Binding Sites / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D012545:Schiff Bases / Q000494:pharmacology*; D013820:Thermolysin / Q000037:antagonists & inhibitors*; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013997:Time Factors
D008024:Ligands; D012545:Schiff Bases; D003035:Cobalt; D013917:Thrombin; D013820:Thermolysin