A5041550637- Peptidase Inhibition and Analysis
- Pneumocystis jirovecii pneumonia detection and treatment
- Galectins and Cancer Biology
- Antifungal resistance and susceptibility
- vaccines and immunoinformatics approaches
- Neuropeptides and Animal Physiology
- Protease and Inhibitor Mechanisms
- Immune Cell Function and Interaction
- Diabetes Treatment and Management
- Glycosylation and Glycoproteins Research
- Cholesterol and Lipid Metabolism
- Neuroendocrine Tumor Research Advances
- Macrophage Migration Inhibitory Factor
- Protein Tyrosine Phosphatases
- SARS-CoV-2 and COVID-19 Research
- Inflammasome and immune disorders
- Biochemical and Molecular Research
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Computational Drug Discovery Methods
- Pneumonia and Respiratory Infections
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Autoimmune and Inflammatory Disorders Research
- Monoclonal and Polyclonal Antibodies Research
- Biotin and Related Studies
National and Kapodistrian University of Athens
1994-2025
National Centre of Scientific Research "Demokritos"
2015-2024
Laboratoire de Biochimie
2023
Institute of Nuclear & Radiological Sciences and Technology, Energy & Safety
2014-2020
University of Crete
2008-2015
Harvard University
2002-2004
University of Massachusetts Chan Medical School
2004
University of Illinois Chicago
1996-2002
Howard Hughes Medical Institute
2002
To determine the location of proteinase in covalent serpin-proteinase complex we prepared seven single-cysteine-containing variants Pittsburgh variant serpin alpha1-proteinase inhibitor, and labeled each cysteine with dansyl fluorophore. The probes were used to proximity trypsin noncovalent complexes serpin, both by direct perturbation fluorescence energy transfer from tryptophans dansyl. Large effects on fluorophores seen for only two positions one position complex. Distances ranging <14 A...
ER aminopeptidase 1 (ERAP1) customizes antigenic peptide precursors for MHC class I presentation and edits the repertoire. Coding single nucleotide polymorphisms (SNPs) in ERAP1 were recently linked with predisposition to autoimmune disease, suggesting a link between pathogenesis of autoimmunity ERAP1-mediated Ag processing. To investigate this possibility, we analyzed effect that disease-linked SNPs have on processing by vitro. Michaelis-Menten analysis revealed presence affects Michaelis...
Significance The human immune system fights disease by eradicating sick cells after first recognizing that they are infected or cancerous. This is achieved specialized detect on the surface of other small molecules called antigenic peptides. Pathogens and cancer can evade stopping generation We designed, synthesized evaluated artificial effectively block a group enzymes key for production destruction show these compounds enhance peptides in reaction toward cancer. Inhibitors this kind may...
Abstract Endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 ERAP2) cooperate to trim antigenic peptide precursors for loading onto MHC class I molecules help regulate the adaptive immune response. Common coding single nucleotide polymorphisms in ERAP1 ERAP2 have been linked with predisposition human diseases ranging from viral bacterial infections autoimmunity cancer. It has hypothesized that altered Ag processing by these enzymes is a causal link disease etiology, but molecular mechanisms...
Endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 cooperate to trim a vast variety of antigenic peptide precursors generate mature epitopes for binding major histocompatibility class I molecules. We report here the first structure determined at 3.08 Å by X-ray crystallography. On basis residual electron density, lysine residue has been modeled in active site enzyme; thus, corresponds an enzyme-product complex. The overall domain organization is highly similar that recently its closed...
ERAP1 (endoplasmic reticulum aminopeptidase 1), ERAP2 and IRAP (insulin-regulated aminopeptidase) are three homologous enzymes that play critical roles in the generation of antigenic peptides. These aminopeptidases excise amino acids from N-terminally extended precursors peptides order to generate correct length epitopes for binding on MHC class I molecules. The specificity these peptidases can affect peptide selection, but has not yet been investigated detail. In present study we utilized a...
Endoplasmic reticulum (ER) aminopeptidases process antigenic peptide precursors to generate epitopes for presentation by MHC class I molecules and help shape the repertoire cytotoxic T-cell responses. To perform this function, ER have recognize a vast variety of sequences. understand how these enzymes substrates, we determined crystal structures aminopeptidase 2 (ERAP2) in complex with substrate analogue peptidic product 2.5 2.7 Å, respectively, compared them apo-form structure 3.0 Å. The...
A novel, multifunctional hydrogel that exhibits a unique set of properties for the effective treatment pancreatic cancer (PC) is presented. The material composed pentablock terpolypeptide type PLys-b-(PHIS-co-PBLG)-PLys-b-(PHIS-co-PBLG)-b-PLys, which noncytotoxic polypeptide. It can be implanted via least invasive route and selectively delivers gemcitabine to efficiently treat PC. Simply mixing novel with an aqueous solution within syringe results in facile formation has ability become...
To determine whether formation of the stable complex between a serpin and target proteinase involves major translocation from its initial position in noncovalent Michaelis complex, we have used fluorescence resonance energy transfer to measure separation fluorescein attached single cysteine on tetramethylrhodamine conjugated proteinase. The interfluorophore was determined for Michaelis-like formed α 1 -proteinase inhibitor (Pittsburgh variant) anhydrotrypsin same trypsin. A difference two...
Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims N-terminally extended antigenic peptide precursors down to mature peptides for presentation by major histocompatibility complex (MHC) class I molecules. ERAP1 has unique properties an being able trim in vitro based on their length and the nature of C-termini.In effort better understand molecular mechanism that uses peptides, we systematically analyzed enzyme's substrate preferences using collections substrates. We discovered strong...
Ankylosing spondylitis (AS) is a chronic systemic arthritic disease that leads to significant disability and loss of quality life in the ∼0.5% worldwide human population it affects. There currently no cure for AS mechanisms underlying its pathogenesis remain unclear. highly genetic, with over 70% genetic risk being associated presence HLA-B27 endoplasmic reticulum aminopeptidase-1 (ERAP1) alleles. Furthermore, gene-gene interactions between ERAP1 alleles have recently been confirmed. Here,...
The oxytocinase subfamily of M1 aminopeptidases, consisting ER aminopeptidase 1 (ERAP1), 2 (ERAP2), and insulin-regulated (IRAP), plays critical roles in the generation antigenic peptides indirectly regulates human adaptive immune responses. We have previously demonstrated that phosphinic pseudotripeptides can constitute potent inhibitors this group enzymes. In study, we used synthetic methodologies able to furnish a series stereochemically defined demonstrate side chains at P1′ P2′...
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an intracellular enzyme that optimizes the peptide cargo of major histocompatibility class I (MHC-I) molecules and regulates adaptive immunity. It has unusual substrate selectivity for length sequence, resulting in poorly understood effects on cellular immunopeptidome. To understand selection by ERAP1, we solved 2 crystal structures with bound transition-state pseudopeptide analogs at 1.68 Å 1.72 Å. Both peptides have their N terminus active...
Endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) metabolizes peptides inside the ER and shapes peptide repertoire available for binding to Major Histocompatibility Complex Class I molecules (MHC-I). However, it may have additional effects on cellular homeostasis, which not been explored. To address these questions, we used both genetic silencing of ERAP1 expression as well treatment with a selective allosteric inhibitor probe changes in immunopeptidome proteome A375 melanoma cancer cell...