Crystal structure of the human angiotensin-converting enzyme–lisinopril complex

摘要: Angiotensin-converting enzyme (ACE) has a critical role in cardiovascular function by cleaving the carboxy terminal His-Leu dipeptide from angiotensin I to produce potent vasopressor octapeptide, II. Inhibitors of ACE are first line therapy for hypertension, heart failure, myocardial infarction and diabetic nephropathy. Notably, these inhibitors were developed without knowledge structure human ACE, but instead designed on basis an assumed mechanistic homology with carboxypeptidase A1. Here we present X-ray testicular its complex one most widely used inhibitors, lisinopril (N2-[(S)-1-carboxy-3-phenylpropyl]-l-lysyl-l-proline; also known as Prinivil or Zestril), at 2.0 A resolution. Analysis three-dimensional shows that it bears little similarity A, resembles neurolysin2 Pyrococcus furiosus carboxypeptidase3—zinc metallopeptidases no detectable sequence ACE. The provides opportunity design domain-selective may exhibit new pharmacological profiles.