Structural insights into the inhibitory mechanism of angiotensin‐I‐converting enzyme by the lactotripeptides IPP and VPP

Author:

Gregory Kyle S.1,Cozier Gyles E.1,Schwager Sylva L. U.2,Sturrock Edward D.2,Acharya K. Ravi1ORCID

Affiliation:

1. Department of Life Sciences University of Bath UK

2. Department of Integrative Biomedical Sciences Institute of Infectious Disease and Molecular Medicine, University of Cape Town South Africa

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.

Funder

Biotechnology and Biological Sciences Research Council

Publisher

Wiley

Subject

Cell Biology,Genetics,Molecular Biology,Biochemistry,Structural Biology,Biophysics

全球学者库

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"全球学者库"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前全球学者库共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2023 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3