Molecular dynamics investigation on the interaction of human angiotensin-converting enzyme with tetrapeptide inhibitors

2021 ◽  
Author(s):  
Xiaoting Liu ◽  
Zheren Wang ◽  
Yawen Gao ◽  
Chunlei Liu ◽  
Ji Wang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Molecular Dynamics ◽  
Angiotensin Converting Enzyme ◽  
Peptide Inhibitors ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Converting Enzyme ◽  
Physiological Functions

Angiotensin-converting enzyme (ACE) is a well-known zinc metalloenzyme whose physiological functions are vital to blood pressure regulation and management of hypertension. The development of more efficient peptide inhibitors is of...

The depressor axis of the renin–angiotensin system and brain disorders: a translational approach

2018 ◽  
Vol 132 (10) ◽  
pp. 1021-1038 ◽  
Author(s):  
Mariela M. Gironacci ◽  
Augusto Vicario ◽  
Gustavo Cerezo ◽  
Mauro G. Silva
Keyword(s):  
Blood Pressure ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Blood Pressure Regulation ◽  
Brain Disorders ◽  
Pressure Regulation ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Brain Functions

All the components of the classic renin–angiotensin system (RAS) have been identified in the brain. Today, the RAS is considered to be composed mainly of two axes: the pressor axis, represented by angiotensin (Ang) II/angiotensin-converting enzyme/AT1 receptors, and the depressor and protective one, represented by Ang-(1–7)/ angiotensin-converting enzyme 2/Mas receptors. Although the RAS exerts a pivotal role on electrolyte homeostasis and blood pressure regulation, their components are also implicated in higher brain functions, including cognition, memory, anxiety and depression, and several neurological disorders. Overactivity of the pressor axis of the RAS has been implicated in stroke and several brain disorders, such as cognitive impairment, dementia, and Alzheimer or Parkinson’s disease. The present review is focused on the role of the protective axis of the RAS in brain disorders beyond its effects on blood pressure regulation. Furthermore, the use of drugs targeting centrally RAS and its beneficial effects on brain disorders are also discussed.

scholarly journals Novel mechanism of inhibition of human angiotensin-I-converting enzyme (ACE) by a highly specific phosphinic tripeptide

2011 ◽  
Vol 436 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Mohd Akif ◽  
Sylva L. Schwager ◽  
Colin S. Anthony ◽  
Bertrand Czarny ◽  
Fabrice Beau ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Active Site ◽  
Phenyl Group ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Structural Determinants ◽  
Dual Inhibitor ◽  
Angiotensin I Converting Enzyme

Human ACE (angiotensin-I-converting enzyme) has long been regarded as an excellent target for the treatment of hypertension and related cardiovascular diseases. Highly potent inhibitors have been developed and are extensively used in the clinic. To develop inhibitors with higher therapeutic efficacy and reduced side effects, recent efforts have been directed towards the discovery of compounds able to simultaneously block more than one zinc metallopeptidase (apart from ACE) involved in blood pressure regulation in humans, such as neprilysin and ECE-1 (endothelin-converting enzyme-1). In the present paper, we show the first structures of testis ACE [C-ACE, which is identical with the C-domain of somatic ACE and the dominant domain responsible for blood pressure regulation, at 1.97Å (1 Å=0.1 nm)] and the N-domain of somatic ACE (N-ACE, at 2.15Å) in complex with a highly potent and selective dual ACE/ECE-1 inhibitor. The structural determinants revealed unique features of the binding of two molecules of the dual inhibitor in the active site of C-ACE. In both structures, the first molecule is positioned in the obligatory binding site and has a bulky bicyclic P1′ residue with the unusual R configuration which, surprisingly, is accommodated by the large S2′ pocket. In the C-ACE complex, the isoxazole phenyl group of the second molecule makes strong pi–pi stacking interactions with the amino benzoyl group of the first molecule locking them in a ‘hand-shake’ conformation. These features, for the first time, highlight the unusual architecture and flexibility of the active site of C-ACE, which could be further utilized for structure-based design of new C-ACE or vasopeptidase inhibitors.

scholarly journals ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuexin Guo ◽  
Boya Wang ◽  
Han Gao ◽  
Lei Gao ◽  
Rongxuan Hua ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Gastrointestinal Tract ◽  
Angiotensin Converting Enzyme ◽  
Host Cells ◽  
Converting Enzyme ◽  
Physiological Functions ◽  
Angiotensin Converting Enzyme 2 ◽  
Important Regulator

The 2019-nCoV is a rapidly contagious pneumonia caused by the recently discovered coronavirus. Although generally the most noticeable symptoms are concentrated in the lungs, the disorders in the gastrointestinal tract are of great importance in the diagnosis of 2019-nCoV. The angiotensin-converting enzyme 2 (ACE2), an important regulator of many physiological functions, including blood pressure and nutrients absorption, is recently identified as a vital entry for 2019-nCoV to enter host cells. In this review, we summarize its functions both physiologically and pathologically. We also elaborate its conflicting roles from the clews of contemporary researches, which may provide significant indications for pharmacological investigations and clinical uses.

Sign in / Sign up

Export Citation Format

Share Document