Structural studies of bradykinin-enhancing peptide precursor protein

• Grant number: 06/01841-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2006
• End date: February 29, 2008
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Raghuvir Krishnaswamy Arni
• Grantee: Karine Fernanda dos Santos
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Angiotensin II, a hypertensive peptide, and bradykinin, a hipotensive peptide, are crucial humoral factors for blood pressure regulation. The key enzyme for this system is angiotensin-converting enzyme (ACE) that produces angiotensin II from angiotensin I and degrades bradykinin. The discovery of the first natural inhibitors for this enzyme, the bradykinin potentiating peptides (BPPs), made it possible to develop the early drugs aimed to control unbalanced cardiovascular functions. Caracteristically, BPPs contain 5 to 13 amino acid residues that have a pyroglutamyl residue at the N-terminal and a proline at the C-terminal. All BBPs, but three short peptides (BPP-5a, BPP-5b e BPP-6a), share similar features including a high content of proline residues and the tripeptide Ile-Pro-Pro at the C-terminus. Until recently, little was known about biogenesis of venom BPP at the molecular level. In 1997, a 1.8-kb cDNA clone was isolated from Bothrops jararaca (Bj) venom gland that encodes a 256-aa precursor for bradykinin-potentiating peptide and a C-type natriuretic peptide (CNP). The precursor protein contains seven BPPs alingned tandemly followed by the CNP peptide. At the present time, the BPPs sum up to 19 peptides described in the venom, venom gland and nervous tissue of Bj. Due to the peculiar organization of these peptides in the precursor protein and the high similarity displayed by the BPPs sequences, the tri-dimensional structure of the precursor seems to provide a novel protein folding. Additionally, structure details should be of relevance in understanding the processing mecanisms involved in BPPs release.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SANTOS, Karine Fernanda dos. Estudos estruturais do precursor dos peptídeos potenciadores de Bradicinina e da proteína nudel: nuclear distribution element-like. 2008. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto São José do Rio Preto.