1O8A

Crystal Structure of Human Angiotensin Converting Enzyme (Native).

1O8A の概要

• エントリーDOI: 10.2210/pdb1o8a/pdb
• 関連するPDBエントリー: 1O86
• 分子名称: ANGIOTENSIN CONVERTING ENZYME, 2-acetamido-2-deoxy-beta-D-glucopyranose, ACETATE ION, ... (7 entities in total)
• 機能のキーワード: metalloprotease, ace, peptidyl dipeptidase, type-i membrane-anchored protein.
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 69724.63

構造登録者

Natesh, R.,Schwager, S.L.U.,Sturrock, E.D.,Acharya, K.R. (登録日: 2002-11-26, 公開日: 2003-02-07, 最終更新日: 2023-12-13)

主引用文献

Natesh, R.,Schwager, S.L.,Sturrock, E.D.,Acharya, K.R.
Crystal structure of the human angiotensin-converting enzyme-lisinopril complex.
Nature, 421:551-554, 2003

PubMed Abstract: Angiotensin-converting enzyme (ACE) has a critical role in cardiovascular function by cleaving the carboxy terminal His-Leu dipeptide from angiotensin I to produce a potent vasopressor octapeptide, angiotensin II. Inhibitors of ACE are a first line of therapy for hypertension, heart failure, myocardial infarction and diabetic nephropathy. Notably, these inhibitors were developed without knowledge of the structure of human ACE, but were instead designed on the basis of an assumed mechanistic homology with carboxypeptidase A. Here we present the X-ray structure of human testicular ACE and its complex with one of the 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 of the three-dimensional structure of ACE shows that it bears little similarity to that of carboxypeptidase A, but instead resembles neurolysin and Pyrococcus furiosus carboxypeptidase--zinc metallopeptidases with no detectable sequence similarity to ACE. The structure provides an opportunity to design domain-selective ACE inhibitors that may exhibit new pharmacological profiles.

PubMed: 12540854
DOI: 10.1038/nature01370

実験手法

X-RAY DIFFRACTION (2 Å)