8QHL

Human Angiotensin-1 converting enzyme N-domain in complex with the lactotripeptide VPP

8QHL の概要

• エントリーDOI: 10.2210/pdb8qhl/pdb
• 分子名称: Angiotensin-converting enzyme, 1,2-ETHANEDIOL, TETRAETHYLENE GLYCOL, ... (16 entities in total)
• 機能のキーワード: angiotensin-i converting enzyme, zinc-dependent endopeptidase, di-peptidyl carboxxypeptidase, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 150677.42

構造登録者

Gregory, K.S.,Cozier, G.E.,Acharya, K.R. (登録日: 2023-09-08, 公開日: 2023-11-22, 最終更新日: 2024-10-09)

主引用文献

Gregory, K.S.,Cozier, G.E.,Schwager, S.L.U.,Sturrock, E.D.,Acharya, K.R.
Structural insights into the inhibitory mechanism of angiotensin-I-converting enzyme by the lactotripeptides IPP and VPP.
Febs Lett., 598:242-251, 2024

PubMed Abstract: Human somatic angiotensin-1-converting enzyme (sACE) is composed of a catalytic N-(nACE) and C-domain (cACE) of similar size with different substrate specificities. It is involved in the regulation of blood pressure by converting angiotensin I to the vasoconstrictor angiotensin II and has been a major focus in the development of therapeutics for hypertension. Bioactive peptides from various sources, including milk, have been identified as natural ACE inhibitors. We report the structural basis for the role of two lacototripeptides, Val-Pro-Pro and Ile-Pro-Pro, in domain-specific inhibition of ACE using X-ray crystallography and kinetic analysis. The lactotripeptides have preference for nACE due to altered polar interactions distal to the catalytic zinc ion. Elucidating the mechanism of binding and domain selectivity of these peptides also provides important insights into the functional roles of ACE.

PubMed: 37904282
DOI: 10.1002/1873-3468.14768

実験手法

X-RAY DIFFRACTION (1.9 Å)