Evidence map›Paper›PMID 10229679›Full record

ArticleThe Biochemical journal1999

Inhibition of ATPase, GTPase and adenylate kinase activities of the second nucleotide-binding fold of the cystic fibrosis transmembrane conductance regulator by genistein.

C Randak, E A Auerswald, I Assfalg-Machleidt, W W Reenstra, W Machleidt

Open access · greenAbstract read
In one paragraph

Article in The Biochemical journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
6.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 62 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

C RandakKinderklinik im Dr. von Haunerschen Kinderspital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, D-80337 München, Germany. Randak@clinbio.med.uni-muenchen.de
E A Auerswald
I Assfalg-Machleidt
W W Reenstra
W Machleidt
Ludwig-Maximilians-Universität München · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In the presence of ATP, genistein, like the ATP analogue adenosine 5'-[beta,gamma-imido]triphosphate (pp[NH]pA), increases cystic fibrosis transmembrane conductance regulator (CFTR) chloride currents by prolonging open times. As pp[NH]pA is thought to increase CFTR currents by interfering with ATP hydrolysis at the second nucleotide-binding fold (NBF-2), the present study was undertaken to investigate the effects of genistein on a fusion protein comprising maltose-binding protein (MBP) and NBF-2 (MBP-NBF-2). MBP-NBF-2 exhibited ATPase, GTPase and adenylate kinase activities that were inhibited by genistein in a partial non-competitive manner with respect to ATP or GTP. Ki values for competitive and uncompetitive inhibition were respectively 20 microM and 63 microM for ATPase, 15 microM and 54 microM for GTPase, and 46 microM and 142 microM for adenylate kinase. For ATPase activity, genistein reduced Vmax by 29% and Vmax/Km by 77%. Additional evidence for complex-formation between genistein and MBP-NBF-2 was obtained by the detection of genistein-dependent alterations in the CD spectrum of MBP-NBF-2 that were consistent with the formation of a higher-ordered state. Addition of MBP-NBF-2 increased the fluorescence intensity of genistein, consistent with a change to a less polar environment. pp[NH]pA partially eliminated this enhanced fluorescence of genistein. These observations provide the first direct biochemical evidence that genistein interacts with CFTR, thus inhibiting NBF-2 activity, and suggest a similar mechanism for genistein-dependent stimulation of CFTR chloride currents.

Indexed as

Adenosine TriphosphatasesAdenylate KinaseAdenylyl ImidodiphosphateBinding SitesCatalysisCatalytic DomainCircular DichroismCystic Fibrosis Transmembrane Conductance RegulatorDimethyl SulfoxideGenisteinGTP PhosphohydrolasesGuanosine TriphosphateHumansIsoflavonesKineticsNucleotidesAdenosine TriphosphatasesAdenylate KinaseAdenylyl ImidodiphosphateCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatordaidzeinDimethyl SulfoxideGenisteinGTP PhosphohydrolasesGuanosine TriphosphateIsoflavonesNucleotidesQuercetinRecombinant Fusion ProteinsSolvents

Identifiers

PMID10229679
PMCPMC1220242
OpenAlexW2047863160

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.