Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Structural Insights into Central Hypertension Regulation by Human Aminopeptidase A

Published: Wednesday, July 31, 2013
Last Updated: Wednesday, July 31, 2013
Bookmark and Share
This study determined the crystal structures of APA complexed with different ligands and calcium.

Abstract
Hypertension is regulated through both  central and systemic renin-angiotensin systems  (RASs). In central RAS, zinc-dependent  aminopeptidase A (APA) up-regulates blood  pressure by specifically cleaving the N-terminal  aspartate, but not the adjacent arginine, from  angiotensin II, a process facilitated by calcium.  Here we determined the crystal structures of  human APA and its complexes with different  ligands, and identified a calcium-binding site in  the S1 pocket of APA. Without calcium, the S1  pocket can bind both acidic and basic residues  through formation of salt bridges with the charged  side chains. In the presence of calcium, the  binding of acidic residues is enhanced as they  ligate the cation, while the binding of basic  residues is no longer favorable due to charge  repulsion. Of the peptidomimetic inhibitors of  APA, amastatin has higher potency than bestatin  by fitting better in the S1 pocket and interacting  additionally with the S3’ subsite. These results  explain the calcium-modulated substrate  specificity of APA in central hypertension  regulation and can guide design and development  of brain-targeting antihypertensive APA  inhibitors.

This study was published online in the Journal of Biological Chemistry and is free to access.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More Than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Sample & Analysis Tracking in Oncogenomic Experiments
The study outlines Onco-STS, a web-based laboratory information management system for sample and analysis tracking in oncogenomic experiments.
Friday, May 08, 2015
Arabidopsis TOE Proteins Involved in the Regulation of Flowering Time
This study found that TOE proteins serve as major integrator of developmental and environmental signaling pathways, especially the photoperiod flowering pathway, triggering flowering at an appropriate age and time.
Wednesday, May 06, 2015
Aflatoxin Biosynthesis - a Novel Source of Reactive Oxygen Species
Researchers at the Michigan State University found that the aflatoxin biosynthetic pathway in A. Parasiticus directly or indirectly generates ROS in aflatoxisomes/endosomes and that Superoxide represents a significant fraction of the aflatoxin biosynthesis-derived ROS pool.
Wednesday, May 06, 2015
SSR Markers and Genetic Diversity in White Birch
The results of this study indicate that the white birch trees sampled from six geographical locations had low to moderate similarity (0.025–0.610) and suggested that the SSR primers used in this study can effectively distinguish white birch germplasm.
Wednesday, May 06, 2015
The Genetics Behind Abdominal Pigmentation in Drosophila melanogaster
This study by researchers at the North Carolina State University provides evidence that genetic variation at a number of steps in regulatory, developmental, and transport pathways may contribute to natural variation in abdominal pigmentation.
Wednesday, May 06, 2015
Selection of Reference Genes for Quantitative RT-PCR Analysis
The expression stability of 12 commonly used reference genes was analysed.
Thursday, April 02, 2015
Improving the Extraction and Recovery of DNA from Cotton Swabs
This study evaluates methods to improve the extraction and recovery of DNA from cotton swabs for forensic analysis.
Tuesday, January 13, 2015
Metabolomics Data Normalization with EigenMS
In this study, a singular value decomposition-based method, called EigenMS, for normalization of metabolomics data was tested.
Wednesday, January 07, 2015
Circadian Variation Of The Human Metabolome
Real-time breath analysis was used to study circadian metabolism.
Wednesday, January 07, 2015
Bridging Quantitative Analysis and Untargeted Metabolomics
Untargeted metabolomics has become a popular tool in metabolite biomarker discovery and in the evaluation of metabolic pathway changes associated with disease.
Thursday, December 04, 2014
Proteomics for Systems Toxicology
MS-based proteomics is maturing into a robust technology for the measurement of proteome-wide exposure effects.
Monday, November 24, 2014
A Continuous Flow System for the Measurement of Ambient Nitrogen Oxides
The proposed method can be used in industrial locations to continuously monitor ambient NOx levels and it can be automated for measuring the variation of NOx concentrations.
Friday, November 14, 2014
Charge-Tagged Proline-Based Organocatalyst for Mechanistic Studies Using ESI-MS
In a comparative continous flow ESI-MS study, researchers use a new charged catalyst and neutral L-proline to investigate the proline-catalyzed inverse crossed aldol reaction of aldehydes with diethyl ketomalonate.
Friday, November 14, 2014
Single-Step Isolation of Extracellular Vesicles by SEC
Researchers from the University of Amsterdam have developed a single-step protocol to isolate vesicles from human body fluids.
Thursday, October 16, 2014
Simple, Rapid and Effective Method for Ammonia Determination
Researchers have a developed a modern, miniaturized and economic flow system to overcome problems of using Nessler's reagent for ammonia determination.
Thursday, October 16, 2014
Scientific News
The Changing Tides of the In Vitro Diagnostics Market
With the increasing focus in personalized medicine, diagnostics plays a crucial role in patient monitoring.
Immunotherapy Agent Benefits Patients with Drug-Resistant Multiple Myeloma in First Human Trial
Daratumumab proved generally safe in patients, even at the highest doses.
Low-level Arsenic Exposure Before Birth Associated with Early Puberty in Female Mice
Study examine whether low-dose arsenic exposure could have similar health outcomes in humans.
Inciting an Immune Attack On Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
‘Mutation-Tracking’ Blood Test for Breast Cancer
Scientists have developed a blood test for breast cancer able to identify which patients will suffer a relapse after treatment, months before tumours are visible on hospital scans.
Cellular Contamination Pathway for Heavy Elements Identified
Berkeley Lab scientists find that an iron-binding protein can transport actinides into cells.
Intensity of Desert Storms May Affect Ocean Phytoplankton
MIT study finds phytoplankton are extremely sensitive to changing levels of desert dust.
Common ‘Heart Attack’ Blood Test May Predict Future Hypertension
Small rises in troponin levels may have value as markers for subclinical heart damage and high blood pressure.
LaVision BioTec Reports on the Neuro Research on the Human Brain After Trauma
Company reports on the work of Dr Ali Ertürk from the Institute for Stroke and Dementia Research at LMU Munich.
NIH Study Shows No Benefit of Omega-3 Supplements for Cognitive Decline
Research was published in the Journal of the American Medical Association.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!