In my logic, any kinase enzymes would need phosphate donor which coming from nucleotide triphosphate. If there is any ligands without phosphate group which also interacts and occupies nucleotide triphosphate's binding site with more affinity than nucleotide triphosphate, does that make those ligands inhibits kinase competitively? Since there is no phosphate donor could interacts with kinase and no phosphate group would be transferred?
There are many, many protein tyrosine and serine/threonine kinase inhibitors that have been described that are competitive inhibitors and occupy the ATP binding site but do not contain a phosphate group. This includes drugs that are in clinical use now. Competitive non-nucleotide kinase inhibitors are a major branch of drug discovery.
Dear Dr. Shapiro,
Thanks for your kind answer, so if I could conclude, no matter kind of interacts occurs, as long as those ligands have affinity towards ATP binding site (especially higher than ATP), so basically the ligand could be classified as kinase inhibitor.
Thanks for advance,
Kind regards,
Mohammad Rizki Fadhil Pratama
To be effective inhibitors of protein kinases in cells when in competition with the millimolar concentration of ATP found in cells, which is usually much higher than the Km for ATP, kinase inhibitors usually require Kis in the low (i.e.single-digit) nanomolar range or lower, and Kis in the picomolar range are common. Another problem for designers of kinase inhibitors, besides affinity, is selectivity. The kinome contains hundreds of enzymes of varying degrees of relatedness. It is very challenging to design compounds that selectively inhibit only one of them.
Dear Dr. Shapiro,
Thanks for your answer again, I got your point. Some of my compound is below single-digit nanomolar which ATP is about two-digit nanomolar. Now I have to find clue about selectivity then. Once again thanks for your answer and have very nice day.
With regards,
Mohammad Rizki Fadhil Pratama
In practical terms,a competitive inhibitor will give an inhibition pattern in which the Vmax will not be altered whereas the Km (measure of affinity ) will be altered to be Km (1+[I]/ki) at fixed enzyme and substrate concentration, while the ligand or inhibitor concentration is varied. The lineweaver-burk plot or the reciprocal plot of 1/Vo vs 1/[S] will clearly demonstrate the afore stated situation. This is applicable where the design of the experiment vis-a-vis compound or inhibitor to be implicated in the study is resolved as was pointed out Dr Shapiro.
- Badges
- Science topic
- Similar topics
- Microbiology
- Assays