Energy Landscape Topography Reveals the Underlying Link Between Binding Specificity and Activity of Enzymes.
Enzyme activity (often quantified by kcat/Km) is the main function of enzyme when it is active against the specific substrate. Higher or lower activities are highly desired for the design of novel enzyme and drug resistance. However, it is difficult to measure the activities of all possible variants and find the "hot-spot" within the limit of experimental time. In this study, we explore the underlying energy landscape of enzyme-substrate interactions and introduce the intrinsic specificity ratio (ISR), which reflects the landscape topography. By studying two concrete systems, we uncover the statistical correlation between the intrinsic specificity and the enzyme activity kcat/Km. This physics-based concept and method show that the energy landscape topography is valuable for understanding the relationship between enzyme specificity and activity. In addition, it can reveal the underlying mechanism of enzyme-substrate actions and has potential applications on enzyme design.
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.
Wen-Ting
WT
Chu
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.|Department of Chemistry &Physics, State University of New York at Stony Brook, Stony Brook, NY, 11794, USA.
Jin
J
Wang
D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D004723:Endorphins / Q000737:chemistry; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000737:chemistry; D010749:Phosphoprotein Phosphatases / Q000737:chemistry; D011485:Protein Binding; D013379:Substrate Specificity; D013816:Thermodynamics
D004723:Endorphins; D010446:Peptide Fragments; C041128:beta-casomorphin 7; D010749:Phosphoprotein Phosphatases