IC50-to-Ki: a web-based tool for converting IC50 to Ki values for inhibitors of enzyme activity and ligand binding
TLDR
A new web-server tool estimates Ki values from experimentally determined IC50 values for inhibitors of enzymes and of binding reactions between macromolecules and ligands to enable end users to help gauge the quality of the underlying assumptions used in these calculations.Abstract:
A new web-server tool estimates Ki values from experimentally determined IC50 values for inhibitors of enzymes and of binding reactions between macromolecules (e.g. proteins, polynucleic acids) and ligands. This converter was developed to enable end users to help gauge the quality of the underlying assumptions used in these calculations which depend on the type of mechanism of inhibitor action and the concentrations of the interacting molecular species. Additional calculations are performed for nonclassical, tightly bound inhibitors of enzyme-substrate or of macromolecule-ligand systems in which free, rather than total concentrations of the reacting species are required. Required userdefined input values include the total enzyme (or another target molecule) and substrate (or ligand) concentrations, the Km of the enzyme-substrate (or the Kd of the target-ligand) reaction, and the IC50 value. Assumptions and caveats for these calculations are discussed along with examples taken from the literature. The host database for this converter contains kinetic constants and other data for inhibitors of the proteolytic clostridial neurotoxins (http:// botdb.abcc.ncifcrf.gov/toxin/kiConverter.jsp).read more
Citations
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Journal ArticleDOI
Structural snapshots of the catalytic cycle of the phosphodiesterase Autotaxin.
Jens Hausmann,Willem-Jan Keune,Agnes L. Hipgrave Ederveen,Leonie van Zeijl,Robbie P. Joosten,Anastassis Perrakis +5 more
TL;DR: A new crystal structure of ATX in complex with orthovanadate (ATX-VO5), which binds the Oγ nucleophile of Thr209 and adopts a trigonal bipyramidal conformation, following the nucleophile attack onto the substrate is presented.
Journal ArticleDOI
Fast NMR Methods for Measuring in the Direct and/or Competition Mode the Dissociation Constants of Chemical Fragments Interacting with a Receptor
TL;DR: In this paper, fast NMR methods for measuring the dissociation constant in direct and competition modes are presented, along with their application to the measurement of the binding affinities of several ligands of the heat shock protein 90.
Journal ArticleDOI
Streptomyces coelicolor XdhR is a direct target of (p)ppGpp that controls expression of genes encoding xanthine dehydrogenase to promote purine salvage.
Smitha Sivapragasam,Anne Grove +1 more
TL;DR: It is proposed that XdhR is a direct target of (p)ppGpp, and that expression of xdhABC is upregulated during the stringent response to promote purine salvage pathways, maintain GTP homeostasis and ensure continued (p).
Journal ArticleDOI
Nanomolar inhibitors of glycogen phosphorylase based on β-D-glucosaminyl heterocycles: a combined synthetic, enzyme kinetic and protein crystallography study
Éva Bokor,Efthimios Kyriakis,Theodora G.A. Solovou,Csenge Koppány,Anastassia L. Kantsadi,Katalin E. Szabó,Andrea Szakács,Georgios A Stravodimos,Tibor Docsa,Vassiliki T. Skamnaki,Spyros E. Zographos,Pál Gergely,Demetres D. Leonidas,László Somsák +13 more
TL;DR: An X-ray crystallography study of the rabbit muscle GPb inhibitor complexes revealed structural features of the strong binding and offered an explanation for the differences in inhibitory potency between glucosyl and glucosaminyl derivatives and also for the Differences between imidazole and 1,2,4-triazole analogues.
Journal ArticleDOI
Structural enzymology and inhibition of the bi-functional folate pathway enzyme HPPK–DHPS from the biowarfare agent Francisella tularensis
Gary X. Shaw,Yue Li,Genbin Shi,Yan Wu,Scott Cherry,D. Needle,Di Zhang,Joseph E. Tropea,David S. Waugh,Honggao Yan,Xinhua Ji +10 more
TL;DR: In this paper, the binding and inhibitory activities of two HPPK inhibitors (HP-18 and HP-26) against F.tularensis (Ft) were elucidated.
References
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Journal ArticleDOI
Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.
TL;DR: The analysis described shows K I does not equal I 50 when competitive inhibition kinetics apply; however, K I is equal to I 50 under conditions of either noncompetitive or uncompetitive kinetics.
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A linear equation that describes the steady-state kinetics of enzymes and subcellular particles interacting with tightly bound inhibitors.
TL;DR: D dose-response measurements generate a linear plot of inhibitor concentration divided by degree of inhibition against velocity without inhibitor divided by velocity with inhibitor, which indicates that the inhibitors of oxidative phosphorylation, rutamycin and bongkrekic acid, are tightly bound to rat liver mitochondria.
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BRENDA, AMENDA and FRENDA the enzyme information system: new content and tools in 2009
TL;DR: The web service via a SOAP (Simple Object Access Protocol) interface for access to the BRENDA data has been further enhanced and a new search option provides the access to protein-specific data.
Journal ArticleDOI
Fluorescence Polarization Competition Assay: The Range of Resolvable Inhibitor Potency Is Limited by the Affinity of the Fluorescent Ligand
TL;DR: The higher the affinity of the fluorescent ligand, the wider the range of inhibitor potency that can be resolved, and an approximate estimate for the low end of inhibitor K(i) values thatCan be resolved is the K(d) value of theorescent ligand.