Porcine pulmonary angiotensin I-converting enzyme—Biochemical characterization and spatial arrangement of the N- and C-domains by three-dimensional electron microscopic reconstruction

Abstract

CitationPorcine pulmonary angiotensin I-converting enzyme--biochemical characterization and spatial arrangement of the N-and C-domains by three-dimensional electron microscopic reconstruction.

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

“…Purified ACE is a single polypeptide of around 150-180 kDa . Recent purification of porcine-lung ACE reported a molecular mass of 170 kDa by SDS-PAGE and 175 kDa by matrix-assisted laser desorption ionization mass spectrometry (Chen et al, 2010). Using this last figure and the known amino acid sequence of porcine ACE, approximately 16% of the mass spectrometry--determined molecular weight is due to glycosylation (http://www.ncbi.nlm.nih.gov/protein/NP_001077410.1).…”

“…Our understanding of ACE structure is further enhanced by 1) the availability of ACE sequence from several species; 2) the three-dimensional crystal structure of the N-domain of ACE, the C-domain, and the enzyme ACE2, which is a C-domain homolog of ACE; and 3) the three-dimensional electron microscopic reconstruction of porcine ACE followed by the fitting of these data to the human atomic models Towler et al, 2004;Corradi et al, 2006;Chen et al, 2010). These studies allow the representation of mature human ACE, as shown in Fig.…”

“…The C-domain is followed by a stalk from approximately Gln1194 to Arg1227, a hydrophobic transmembrane domain from Val1228 to Ser1248, and an intracellular C-terminal tail from Gln1249 to Ser1277 at the end of the molecule. Limited proteolysis of ACE with endoproteinase Asp-N will cleave between the Thr615-Asp616 and the Leu1219-Asp1220 peptide bonds to generate the two catalytic domains in active form that can be separated by a lisinopril affinity column Chen et al, 2010). Several groups have suggested that in somatic ACE, the catalytic activity of the C-domain is negatively regulated by the presence of the N-domain (Binevski et al, 2003;Woodman et al, 2005).…”

“…Model of human somatic ACE. This model is a three-dimensional reconstruction of the electron microscopic appearance of porcine somatic ACE (the net) combined with available human X-ray crystal structures (Chen et al, 2010;Danilov et al, 2011). It shows the ACE N-domain (Leu1-Pro601), linker region (Pro602-Asp612), C-domain (Leu613--Pro1193), stalk region (Gln1194-Arg1227), transmembrane segment (Val1228-Ser1248), and intracellular domain (Gln1249-Ser1277) Corradi et al, 2006).…”

Structural Characteristics and Antihypertensive Effects of Angiotensin-Iconverting Enzyme Inhibitory Peptides in the Renin-Angiotensin and Kallikrein Kinin Systems

“…According to Chen et al (2010), the somatic angiotensin-I-converting enzyme (sACE) isolated from the pig lung had a molecular weight of 180 kDa. Upon the proteolytic cleavage, two fragments with the size of about 90 kDa were attained and identified by amino-terminal sequence analysis and later known as N-and C-domains of sACE where each domain comprises a functional Zn 2+ binding active centre (Danilov et al, 2014).…”