[Structure and physiological significance of angiotensin converting enzyme domains]

Somatic angiotensin converting enzyme (ACE) consists of two homologous catalytic domains (N- and C-domain), each of which bears an active site exhibiting different biochemical properties. The ACE isoforms consisted of one domain were also detected in mammals. Substantial progress in ACE domain research was achieved during the last years, when crystal their structures were determined. The crystal structures of domains in complex with diverse potent ACE inhibitors provided new insights into structure-based differences of the domain active sites. Physiological functions of ACE are not limited by regulation of the cardiovascular system. Recent evidence suggests that the ACE domains may be also involved into control distinct physiological functions. The C-terminal catalytic domain, playing important role in regulation of blood pressure, catalyzes angiotensin I cleavage in vivo. The N-domain contributes to processing of other bioactive peptides for which it exhibits high affinity. Domain-selective inhibitors able to block selectively either the N- or C-domain of ACE have been developed.