Evidence map›Paper›PMID 26931059›Full record

ArticleScientific reports2016

N-terminal domain of Bothrops asper Myotoxin II Enhances the Activity of Endothelin Converting Enzyme-1 and Neprilysin.

A Ian Smith, Niwanthi W Rajapakse, Oded Kleifeld, Bruno Lomonte, Nkumbu L Sikanyika, Alexander J Spicer, Wayne C Hodgson, Paul J Conroy, David H Small, David M Kaye and 3 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

4 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

A Ian SmithDepartment of Biochemistry &Molecular Biology, Biomedical Discovery Institute, Monash University, Clayton, Vic 3800, Australia.
Niwanthi W RajapakseBaker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, Victoria 3004, Australia.
Oded KleifeldDepartment of Biochemistry &Molecular Biology, Biomedical Discovery Institute, Monash University, Clayton, Vic 3800, Australia.
Bruno LomonteInstituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Nkumbu L SikanyikaDepartment of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, Vic 3800, Australia.
Alexander J SpicerDepartment of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, Vic 3800, Australia.
Wayne C HodgsonDepartment of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, Vic 3800, Australia.
Paul J ConroyDepartment of Biochemistry &Molecular Biology, Biomedical Discovery Institute, Monash University, Clayton, Vic 3800, Australia.
David H SmallMenzies Research Institute, University of Tasmania, Hobart, Tasmania 7000, Australia.
David M KayeBaker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, Victoria 3004, Australia.
Helena C ParkingtonDepartment of Physiology, Biomedical Discovery Institute, Monash University, Clayton, Vic 3800, Australia.
James C WhisstockDepartment of Biochemistry &Molecular Biology, Biomedical Discovery Institute, Monash University, Clayton, Vic 3800, Australia.
Sanjaya KuruppuDepartment of Biochemistry &Molecular Biology, Biomedical Discovery Institute, Monash University, Clayton, Vic 3800, Australia.
Monash University · AUAustralian Regenerative Medicine Institute · AUBaker Heart and Diabetes Institute · AUUniversidad de Costa Rica · CRUniversity of Tasmania · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neprilysin (NEP) and endothelin converting enzyme-1 (ECE-1) are two enzymes that degrade amyloid beta in the brain. Currently there are no molecules to stimulate the activity of these enzymes. Here we report, the discovery and characterisation of a peptide referred to as K49-P1-20, from the venom of Bothrops asper which directly enhances the activity of both ECE-1 and NEP. This is evidenced by a 2- and 5-fold increase in the Vmax of ECE-1 and NEP respectively. The K49-P1-20 concentration required to achieve 50% of maximal stimulation (AC50) of ECE-1 and NEP was 1.92 ± 0.07 and 1.33 ± 0.12 μM respectively. Using BLITZ biolayer interferometry we have shown that K49-P1-20 interacts directly with each enzyme. Intrinsic fluorescence of the enzymes change in the presence of K49-P1-20 suggesting a change in conformation. ECE-1 mediated reduction in the level of endogenous soluble amyloid beta 42 in cerebrospinal fluid is significantly higher in the presence of K49-P1-20 (31 ± 4% of initial) compared with enzyme alone (11 ± 5% of initial; N = 8, P = 0.005, unpaired t-test). K49-P1-20 could be an excellent research tool to study mechanism(s) of enzyme stimulation, and a potential novel drug lead in the fight against Alzheimer's disease.

Indexed as

AlanineAmino Acid SequenceEndothelin-Converting EnzymesEnzyme ActivationEnzyme AssaysGroup II Phospholipases A2HEK293 CellsHumansKineticsNeprilysinPeptidesProtein DomainsReptilian ProteinsStructure-Activity RelationshipAlanineEndothelin-Converting EnzymesGroup II Phospholipases A2myotoxin II, Bothrops asperNeprilysinPeptidesReptilian Proteins

Identifiers

PMID26931059
PMCPMC4773759
OpenAlexW2292754188

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.