Comment on “Binding Affinity Determines Substrate Specificity and Enables Discovery of Substrates for N-Myristoyltransferases”

Establishing the protein posttranslational modification (PTM) landscape at proteome scale relies on target specificity of relevant enzyme catalysts. Su et al. [ ACS Catal. 2021, 11, 14877] proposed that “the kcat/Km value is not best parameter to determine in vivo substrate an enzyme. Instead, binding affinities substrates are more important for determining enzymes a physiological setting”. The authors extended their conclusions any “substrate pairs catalyze PTM”. This study provides springboard discussion relative merits different approaches used identify targets. My point view constant remains highly defining specificity, while knowledge catalytic mechanism─ including limiting and synergistic steps─is crucial reliable data interpretation. Enzyme catalysis cannot be reduced solely formation encountered complex makes reaction between two partners likely. I highlight how reactants promote conformational changes significantly contribute final whose impact can only assessed using kinetic approaches. There also need integrate with availability each competing substrate, resources must regularly updated validate PTM discovery. These apply catalyst.