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Identification of e...
Identification of enzyme inhibitory mechanisms from steady-state kinetics
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- Fange, David (författare)
- Uppsala universitet,Struktur- och molekylärbiologi
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Lovmar, Martin (författare)
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- Pavlov, Michael Y. (författare)
- Uppsala universitet,Struktur- och molekylärbiologi
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- Ehrenberg, Måns (författare)
- Uppsala universitet,Struktur- och molekylärbiologi
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(creator_code:org_t)
- Elsevier BV, 2011
- 2011
- Engelska.
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Ingår i: Biochimie. - : Elsevier BV. - 0300-9084 .- 1638-6183. ; 93:9, s. 1623-1629
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Enzyme inhibitors are used in many areas of the life sciences, ranging from basic research to the combat of disease in the clinic. Inhibitors are traditionally characterized by how they affect the steady-state kinetics of enzymes, commonly analyzed on the assumption that enzyme-bound and free substrate molecules are in equilibrium. This assumption, implying that an enzyme-bound substrate molecule has near zero probability to form a product rather than dissociate, is valid only for very inefficient enzymes. When it is relaxed, more complex but also more information-rich steady-state kinetics emerges. Although solutions to the general steady-state kinetics problem exist, they are opaque and have been of limited help to experimentalists. Here we reformulate the steady-state kinetics of enzyme inhibition in terms of new parameters. These allow for assessment of ambiguities of interpretation due to kinetic scheme degeneracy and provide an intuitively simple way to analyze experimental data. We illustrate the method by concrete examples of how to assess scheme degeneracy and obtain experimental estimates of all available rate and equilibrium constants. We suggest simple, complementary experiments that can remove ambiguities and greatly enhance the accuracy of parameter estimation.
Nyckelord
- Michaelis-Menten kinetics
- Non-competitive inhibitor
- Uncompetitive inhibitor
- Mixed inhibitor
- Parameter estimation
- Enzyme activation
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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