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N‐terminal domain of Bothrops asper Myotoxin II Enhances the Activity of Endothelin Converting Enzyme and Neprilysin
Author(s) -
Kuruppu Sanjaya,
Rajapakse Niwanthi,
Kleifeld Oded,
Small David H,
Whisstock James,
Smith Alexander Ian
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.606.4
Subject(s) - neprilysin , enzyme , chemistry , pharmacology , biochemistry , medicine
Neprilysin (NEP) and endothelin converting enzyme (ECE) are two enzymes that clear 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 and NEP. This is evidenced by a 1.8‐ and 5.6‐fold increase in the Vmax of ECE and NEP respectively. The K49‐P1‐20 concentration required to achieve 50% of maximal stimulation (AC 50 ) of ECE and NEP was 4.2 ± 0.2 and 2.9 ± 0.3 ng/μL respectively. Increase in activity is the result of a conformational change in the enzyme that occurs upon K49‐P1‐20 binding. Therefore, K49‐P1‐20 is both an excellent research tool to study enzyme activation, and a potential novel drug lead in the fight against Alzheimer's disease. Support or Funding Information This work was supported by funding made available through 1) the strategic grant scheme administered by the Monash University's Faculty of Medicine Nursing & Health Sciences; 2) Monash University's Interdisciplinary Research Funding Scheme; and 3) ANZ National Medical Foundation