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 K_off.[2]

The Michaelis-Menten constant is denoted by K_m and is represented by the equation K_m= (K_off + K_cat)/ K_on. The rates that the enzyme binds and dissociates from the substrate are represented by K_on and K_off respectively. K_m 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. It is important to know that K_m and K_off are proportional, thus at higher levels of dissociation, the Michaelis-Menten constant will be larger.[4]

References

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.
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, Shlomi; Urbakh, Michael; Klafter, Joseph (March 2014). "Role of substrate unbinding in Michaelis—Menten enzymatic reactions". National Academy of Sciences of the United States of America. 111: 4391–4396. PMC 3970482 – via JSTOR.
Copeland, Robert Allen (2000). Enzymes a practical introduction to structure, mechanism, and data analysis. Wiley Library Catalog: J. Wiley. pp. 76–81.

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[Wanner_2007-1] 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.

[Berezhkovskii_2017-2] 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.

[3] Reuveni, Shlomi; Urbakh, Michael; Klafter, Joseph (March 2014). "Role of substrate unbinding in Michaelis—Menten enzymatic reactions". National Academy of Sciences of the United States of America. 111: 4391–4396. PMC 3970482 – via JSTOR.

[4] Copeland, Robert Allen (2000). Enzymes a practical introduction to structure, mechanism, and data analysis. Wiley Library Catalog: J. Wiley. pp. 76–81.