The peculiar characteristics of the amino acid sequence of angiotensin I-converting enzyme, as determined by cDNA cloning of the human endothelial enzyme.
The angiotensin-I converting enzyme (ACE) is a membrane bound zinc metallopeptidase of the vascular endothelial cell. Recently, the complete amino-acid sequence of human ACE has been determined by protein sequencing and cDNA cloning in endothelial cell libraries. The ACE is encoded from a 4.3 kb transcript and comprises 1,306 amino acids. The molecule comprises a signal peptide of 29 residues cleaved off during maturation. It is most likely anchored by a short transmembrane domain situated near the carboxyterminal extremity. Interestingly, the molecule presents a high degree of internal homology between two large peptidic domains. Each of these domains contains short sequences identical to zinc binding and active site sequences of other zinc metallopeptidases and therefore bears a putative active site. The ACE gene results probably from duplication and fusion of a more ancestral gene, coding for a putative nonduplicated enzyme. However, despite the duplicated structure of ACE, it has been reported that there is only one zinc atom bound per molecule. Competitive inhibitors seem to interact with a unique high affinity binding site. Therefore, there is only one active site in ACE whose location remains to be determined.
Alhenc-Gélas
F
F
INSERM U36, Paris, France.
Soubrier
F
F
Hubert
C
C
Allegrini
J
J
Corvol
P
P
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis*; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000032:analysis* / Q000235:genetics; D012995:Solubility
D004247:DNA; D007703:Peptidyl-Dipeptidase A