ArticleThe Journal of biological chemistry2013
Structural insights into central hypertension regulation by human aminopeptidase A.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- LigExtract: Large-scale Automated Identification of Ligands from Protein Structures in the Protein Data Bank.Genomics, proteomics & bioinformatics · 2025Article
- Biomarkers in Renal Cell Carcinoma: A Systematic Review and Immunohistochemical Validation Study.Cancers · 2025Article
- Exploring Similarities and Differences Between Methods That Exploit Patterns of Local Genetic Correlation to Identify Shared Causal Loci Through Application to Genome-Wide Association Studies of Multiple Long Term Conditions.Genetic epidemiology · 2025Article
- Quantum Mechanics/Molecular Mechanics Simulations Distinguish Insulin-Regulated Aminopeptidase Substrate (Oxytocin) and Inhibitor (Angiotensin IV) and Reveal Determinants of Activity and Inhibition.Journal of chemical information and modeling · 2025Article
- Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets.Nature communications · 2024Article
- Bioinformatic characterization of ENPEP, the gene encoding a potential cofactor for SARS-CoV-2 infection.PloS one · 2024Article
- Marine Invertebrates: A Promissory Still Unexplored Source of Inhibitors of Biomedically Relevant Metallo Aminopeptidases Belonging to the M1 and M17 Families.Marine drugs · 2023Review
- Article
- Differential N-terminal processing of beta and gamma actin.iScience · 2022Article
- Regulation of zinc-dependent enzymes by metal carrier proteins.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Review
- Can ERAP1 and ERAP2 Form Functional Heterodimers? A Structural Dynamics Investigation.Frontiers in immunology · 2022Article
- Structural and Functional Basis of Potent Inhibition of Leishmanial Leucine Aminopeptidase by Peptidomimetics.ACS omega · 2021Article
- P1' Residue-Oriented Virtual Screening for Potent and Selective Phosphinic (Dehydro) Dipeptide Inhibitors of Metallo-Aminopeptidases.Biomolecules · 2020Article
- IRAP Inhibitors: M1-Aminopeptidase Family Inspiration.Frontiers in pharmacology · 2020Review
- Structural characterization of plasmodial aminopeptidase: a combined molecular docking and QSAR-based in silico approaches.Molecular diversity · 2019Article
- Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure.Pharmacological reviews · 2019Review
- Connexin37-Dependent Mechanisms Selectively Contribute to Modulate Angiotensin II -Mediated Hypertension.Journal of the American Heart Association · 2019Article
- Discovery of novel non-competitive inhibitors of mammalian neutral M1 aminopeptidase (APN).Biochimie · 2017Article
- M1 aminopeptidases as drug targets: broad applications or therapeutic niche?The FEBS journal · 2017Review
- Aminopeptidase A initiates tumorigenesis and enhances tumor cell stemness via TWIST1 upregulation in colorectal cancer.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, 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, whereas 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 the design and development of brain-targeting antihypertensive APA inhibitors.
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