Spectroscopic and structural analysis of somatic and N-domain angiotensin I-converting enzyme isoforms from mesangial cells from Wistar and spontaneously hypertensive rats

M C C de Andrade, R Affonso, F B Fernandes, A C Febba, Idcg da Silva, R C R Stella, O Marson, G N Jubilut, I Y Hirata, A K Carmona, Hazel Corradi, K Ravi Acharya, E D Sturrock, D E Casarini

Research output: Contribution to journalArticle

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Abstract

Angiotensin I-converting enzyme (ACE) plays a key role in the renin-angiotesin aldosterone cascade. We analysed the secondary structure and structural organization of a purified 65 kDa N-domain ACE (nACE) from Wistar rat mesangial cells, a 90 kDa nACE from spontaneously hypertensive rats and a 130 kDa somatic ACE. The C-terminal alignment of the 65 kDa nACE with rat ACE revealed that the former was truncated at Ser(482), and the sequence of the 90 kDa nACE ended at Pro(629). Protein's secondary structure consisted predominantly of a-helices. The 90 and 65 kDa isoforms were the most stable in guanidine and at low pH, respectively. Enzymatic activity decreased with loss in secondary structure, except in the case of guanidine HCl where the 90 kDa fragment loses its secondary structure faster than its enzymatic activity. We identified and characterized the activity and stability of these isoforms and these findings would be helpful on the understanding of the role of nACE isoforms in hypertension.
Original languageEnglish
Pages (from-to)238-243
Number of pages6
JournalInternational Journal of Biological Macromolecules
Volume47
Issue number2
DOIs
Publication statusPublished - 1 Aug 2010

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Spectroscopic analysis
Mesangial Cells
Peptidyl-Dipeptidase A
Inbred SHR Rats
Structural analysis
Rats
Protein Isoforms
Guanidine
Secondary Protein Structure
Aldosterone
Renin
Wistar Rats
Hypertension
Proteins

Keywords

  • structure analysis
  • hypertension
  • N-domain ACE isoforms
  • circular dichroism
  • inhibitor design
  • angiotensin I-converting enzyme

Cite this

Spectroscopic and structural analysis of somatic and N-domain angiotensin I-converting enzyme isoforms from mesangial cells from Wistar and spontaneously hypertensive rats. / de Andrade, M C C; Affonso, R; Fernandes, F B; Febba, A C; da Silva, Idcg; Stella, R C R; Marson, O; Jubilut, G N; Hirata, I Y; Carmona, A K; Corradi, Hazel; Acharya, K Ravi; Sturrock, E D; Casarini, D E.

In: International Journal of Biological Macromolecules, Vol. 47, No. 2, 01.08.2010, p. 238-243.

Research output: Contribution to journalArticle

de Andrade, MCC, Affonso, R, Fernandes, FB, Febba, AC, da Silva, I, Stella, RCR, Marson, O, Jubilut, GN, Hirata, IY, Carmona, AK, Corradi, H, Acharya, KR, Sturrock, ED & Casarini, DE 2010, 'Spectroscopic and structural analysis of somatic and N-domain angiotensin I-converting enzyme isoforms from mesangial cells from Wistar and spontaneously hypertensive rats', International Journal of Biological Macromolecules, vol. 47, no. 2, pp. 238-243. https://doi.org/10.1016/j.ijbiomac.2010.04.015
de Andrade, M C C ; Affonso, R ; Fernandes, F B ; Febba, A C ; da Silva, Idcg ; Stella, R C R ; Marson, O ; Jubilut, G N ; Hirata, I Y ; Carmona, A K ; Corradi, Hazel ; Acharya, K Ravi ; Sturrock, E D ; Casarini, D E. / Spectroscopic and structural analysis of somatic and N-domain angiotensin I-converting enzyme isoforms from mesangial cells from Wistar and spontaneously hypertensive rats. In: International Journal of Biological Macromolecules. 2010 ; Vol. 47, No. 2. pp. 238-243.
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