Dissociation rate
The dissociation rate in chemistry, biochemistry, and pharmacology is the rate or speed at which a ligand dissociates from a protein, for instance, a receptor.[1] It is an important factor in the binding affinity and intrinsic activity (efficacy) of a ligand at a receptor.[1] The dissociation rate for a particular substrate can be applied to enzyme kinetics, including the Michaelis-Menten model.[2] Substrate dissociation rate contributes to how large or small the enzyme velocity will be.[2] In the Michaelis-Menten model, the enzyme binds to the substrate yielding an enzyme substrate complex, which can either go backwards by dissociating or go forward by forming a product.[2] The dissociation rate constant is defined using Koff.[2]
The Michaelis-Menten constant is denoted by Km and is represented by the equation Km= (Koff + Kcat)/ Kon[definition needed]. The rates that the enzyme binds and dissociates from the substrate are represented by Kon and Koff respectively. Km is also defined as the substrate concentration at which enzymatic velocity reaches half of its maximal rate.[3] The tighter a ligand binds to a substrate, the lower the dissociation rate will be. Km and Koff are proportional, thus at higher levels of dissociation, the Michaelis-Menten constant will be larger.[4]
Direct measurements using electrospray ionization mass spectrometry (ESI-MS) have quantified dissociation rate constants for high-affinity ligand-protein interactions, such as the biotin-streptavidin system, offering a deeper understanding of enzyme-substrate dynamics.[5] Recent computational studies have provided insights into the diffusional processes that influence the dissociation rates of bio-molecular complexes, highlighting the importance of molecular movement and binding specificity in these interactions, the importance is considering both the physical movement of molecules and their binding specificities when analyzing dissociation rates.[6]
References[edit]
- ^ a b Wanner K, Höfner G (27 June 2007). Mass Spectrometry in Medicinal Chemistry: Applications in Drug Discovery. John Wiley & Sons. pp. 142–156. ISBN 978-3-527-61091-4.
- ^ a b c d Berezhkovskii AM, Szabo A, Rotbart T, Urbakh M, Kolomeisky AB (April 2017). "Dependence of the Enzymatic Velocity on the Substrate Dissociation Rate". The Journal of Physical Chemistry B. 121 (15): 3437–3442. doi:10.1021/acs.jpcb.6b09055. PMC 5577799. PMID 28423908.
- ^ Reuveni S, Urbakh M, Klafter J (March 2014). "Role of substrate unbinding in Michaelis-Menten enzymatic reactions". Proceedings of the National Academy of Sciences of the United States of America. 111 (12): 4391–6. Bibcode:2014PNAS..111.4391R. doi:10.1073/pnas.1318122111. PMC 3970482. PMID 24616494.
- ^ Copeland RA (2000). Enzymes a practical introduction to structure, mechanism, and data analysis. Wiley Library Catalog: J. Wiley. pp. 76–81.
- ^ Deng, Lu; Kitova, Elena N.; Klassen, John S. (2013-01-01). "Dissociation Kinetics of the Streptavidin–Biotin Interaction Measured Using Direct Electrospray Ionization Mass Spectrometry Analysis". Journal of the American Society for Mass Spectrometry. 24 (1): 49–56. Bibcode:2013JASMS..24...49D. doi:10.1007/s13361-012-0533-5. ISSN 1044-0305. PMID 23247970.
- ^ Mereghetti, Paolo; Kokh, Daria; McCammon, J Andrew; Wade, Rebecca C (December 2011). "Diffusion and association processes in biological systems: theory, computation and experiment". BMC Biophysics. 4 (1): 2. doi:10.1186/2046-1682-4-2. ISSN 2046-1682. PMC 3093674. PMID 21595997.
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