SgmlV1, France, Analysis, bibRecord, 000311

Intrinsic Activity at the Molecular Level: E. J. Ariëns' Concept Visualized

Identifieur interne : 000311 ( France/Analysis ); précédent : 000310; suivant : 000312

Intrinsic Activity at the Molecular Level: E. J. Ariëns' Concept Visualized

Auteurs : Donald J. Abraham [États-Unis] ; Jean Kister [France] ; Gajanan S. Joshi [États-Unis] ; Michael C. Marden [France] ; Claude Poyart [France]

Source :

Journal of Molecular Biology [ 0022-2836 ] ; 1995.

RBID : ISTEX:BE75F07EC89BE529F815FEC5EAE90EE30A452A78

English descriptors

Abstract

Abstract: The concept of using affinity and intrinsic activity to analyze drug interactions with receptors has had a long history in pharmacological studies. In the simplest case, the biological response will be proportional to the amount of drug bound, i.e. its affinity. However, the biological response is also mediated by the ability of a drug when bound to exert its maximum effectiveness. This effectiveness is termed the intrinsic activity. Physicochemical processes have been thought to be at the basis of intrinsic activity. Detailed oxygen and solution binding experiments combined with X-ray crystallographic studies on allosteric effectors to hemoglobin demonstrate that these potential drug agents bind at the same site in hemoglobin with similar binding constants yet shift the allosteric equilibrium and the oxygen affinity of the T-structure by different degrees. Therefore some of the effectors with similar binding affinities for the same site exhibit varying degrees of affectiveness, i.e. they possess different intrinsic activities. The intrinsic activity of the effector is defined as the ratio of the oxygen affinity constant to the T-state with drug/oxygen affinity constant to the T-state without drug (KT+drug)/(KT control). The source of the intrinsic activity appears to be the ability of the effectors to interact with key residues such as Lys99α at the binding site. These results suggest a general molecular mechanism for allosteric effector modulation of hemoglobin function that might be of use in other allosteric enzyme systems.

Url:

https://api.istex.fr/ark:/67375/6H6-RHR45HF1-5/fulltext.pdf

DOI: 10.1006/jmbi.1995.0265

Affiliations:

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ISTEX:BE75F07EC89BE529F815FEC5EAE90EE30A452A78

Le document en format XML

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<term>Chem</term>
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<term>Effector</term>
<term>Effector activity</term>
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<term>Groupd series</term>
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<term>Hill plot</term>
<term>Human hemoglobin</term>
<term>Hydrophobic interactions</term>
<term>Inositol hexaphosphate</term>
<term>Intrinsic</term>
<term>Intrinsic activity</term>
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<term>Similar binding constants</term>
<term>Simplest case</term>
<term>Small effect</term>
<term>Sodium dithionite</term>
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<term>Standard error</term>
<term>Subunit</term>
<term>Tetramera kaffb</term>
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<front><div type="abstract" xml:lang="en">Abstract: The concept of using affinity and intrinsic activity to analyze drug interactions with receptors has had a long history in pharmacological studies. In the simplest case, the biological response will be proportional to the amount of drug bound, i.e. its affinity. However, the biological response is also mediated by the ability of a drug when bound to exert its maximum effectiveness. This effectiveness is termed the intrinsic activity. Physicochemical processes have been thought to be at the basis of intrinsic activity. Detailed oxygen and solution binding experiments combined with X-ray crystallographic studies on allosteric effectors to hemoglobin demonstrate that these potential drug agents bind at the same site in hemoglobin with similar binding constants yet shift the allosteric equilibrium and the oxygen affinity of the T-structure by different degrees. Therefore some of the effectors with similar binding affinities for the same site exhibit varying degrees of affectiveness, i.e. they possess different intrinsic activities. The intrinsic activity of the effector is defined as the ratio of the oxygen affinity constant to the T-state with drug/oxygen affinity constant to the T-state without drug (KT+drug)/(KT control). The source of the intrinsic activity appears to be the ability of the effectors to interact with key residues such as Lys99α at the binding site. These results suggest a general molecular mechanism for allosteric effector modulation of hemoglobin function that might be of use in other allosteric enzyme systems.</div>
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Intrinsic Activity at the Molecular Level: E. J. Ariëns' Concept Visualized

Intrinsic Activity at the Molecular Level: E. J. Ariëns' Concept Visualized

Source :

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri