A5103249218- Angiogenesis and VEGF in Cancer
- Axon Guidance and Neuronal Signaling
- Poisoning and overdose treatments
- Lipid metabolism and disorders
- Forensic Toxicology and Drug Analysis
- Cancer-related gene regulation
- Foreign Body Medical Cases
- Enzyme Structure and Function
- Airway Management and Intubation Techniques
- Cancer, Hypoxia, and Metabolism
- Tracheal and airway disorders
- Protein Kinase Regulation and GTPase Signaling
- Mycotoxins in Agriculture and Food
- Pharmacological Effects and Toxicity Studies
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- Epilepsy research and treatment
- Analytical Methods in Pharmaceuticals
- Microbial Metabolic Engineering and Bioproduction
- Human Health and Disease
- Carcinogens and Genotoxicity Assessment
- Genomics, phytochemicals, and oxidative stress
- Porphyrin Metabolism and Disorders
- Apelin-related biomedical research
- Pharmacogenetics and Drug Metabolism
Military Medical Academy
2013-2025
University College London
2012-2024
Wolfson Foundation
2024
University of Defence
2024
Institute of Structural and Molecular Biology
2010-2022
University of Novi Sad
2018
Washington Poison Center
2016
UCL Australia
2014
Klinički centar Niš
2013
Institut Sains dan Teknologi Al-Kamal
2009
We report the molecular design and synthesis of EG00229, 2, first small molecule ligand for VEGF-A receptor neuropilin 1 (NRP1) structural characterization NRP1-ligand complexes by NMR spectroscopy X-ray crystallography. Mutagenesis studies localized binding in NRP1 b1 domain a peptide fragment was shown to bind at same site NMR, providing basis design. Compound 2 demonstrated inhibition attenuated VEGFR2 phosphorylation endothelial cells. Inhibition migration cells also observed. The...
The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic pressure, and the reactivity of leukocytes platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, stroke. Herein, we evaluated mice with endothelial-specific deletion Nppc, which encodes C-type natriuretic peptide (CNP), determined this mediator is essential for multiple...
We report the x-ray crystal structure of methylesterase CheB, a phosphorylation-activated response regulator involved in reversible modification bacterial chemotaxis receptors. Methylesterase CheB and methyltransferase CheR modulate signaling output receptors by controlling level receptor methylation. The which consists an N-terminal regulatory domain C-terminal catalytic joined linker, was solved molecular replacement methods using independent search models for two domains. In...
We report the design, synthesis, and biological evaluation of some potent small-molecule neuropilin-1 (NRP1) antagonists. NRP1 is implicated in immune response to tumors, particularly Treg cell fragility, required for PD1 checkpoint blockade. The design these compounds was based on a previously identified compound EG00229. molecules informed supported by X-ray crystal structures. Compound 1 (EG01377) as having properties suitable further investigation. then tested several vitro assays shown...
Abstract Introduction Qualitative and quantitative testing of ethanol in post-mortem samples is an important analytical procedure that provides accurate, precise, reliable results. Given the complexity issue, obtaining a realistic picture lifelong alcoholemia requires supporting blood findings with analyses alternative samples, primarily vitreous humor (VH). Objective The objective this study was to develop validate headspace gas chromatography flame ionization detection (HS/GC-FID) method...
The crystal structure of butyryl-CoA dehydrogenase (BCAD) from Megasphaera elsdenii complexed with acetoacetyl-CoA has been solved at 2.5 A resolution. enzyme crystallizes in the P422 space group cell dimensions a = b 107.76 and c 153.67 A. BCAD is bacterial analog short chain acyl-CoA mammalian mitochondria. Mammalian dehydrogenases are flavin adenine dinucleotide (FAD)-containing enzymes that catalyze first step beta-oxidation fatty acids. Although specific for substrate lengths, they...
Neuropilins (NRPs) are single-pass transmembrane receptors involved in several signaling pathways that regulate key physiological processes such as vascular morphogenesis and axon guidance. The MAM domain of NRP, which has previously been implicated receptor multimerization, was the only portion ectopic NRPs for structure, until now, elusive. Using site-directed mutagenesis linker region preceding we generated a protein construct amenable to crystallization. Here present crystal structure...
NT-26 is a chemolithoautotrophic arsenite oxidizer. Understanding the mechanisms of signalling, tolerance and oxidation by will have significant implications for its use in bioremediation sensing. We identified histidine kinase (AroS) cognate response regulator (AroR) involved arsenite-dependent transcriptional regulation oxidase aroBA operon. AroS contains single periplasmic sensory domain that linked through transmembrane helices to HAMP transmits signal core protein. AroR belongs family...
Neuropilin‐1 ( NRP 1) is a transmembrane co‐receptor involved in binding interactions with variety of ligands and receptors, including receptor tyrosine kinases. Expression 1 several cancers correlates cancer stages poor prognosis. Thus, has been considered therapeutic target the focus multiple drug discovery initiatives. Vascular endothelial growth factor VEGF ) binds to b1 domain through between C‐terminal arginine residues 1‐binding site Tyr297, Tyr353, Asp320, Ser346 Thr349. We obtained...
Abstract Pathological healing characterized by abnormal angiogenesis presents a serious burden to patients’ quality of life requiring innovative treatment strategies. Glycosaminoglycans (GAG) are important regulators angiogenic processes. This experimental and computational study revealed how sulfated GAG derivatives (sGAG) influence the interplay vascular endothelial growth factor (VEGF) 165 its heparin-binding domain (HBD) with signaling receptor VEGFR-2 up atomic detail. There was...
The aim of this study was to analyze data on gabapentinoid-related attendances the National Poison Control Center Serbia (NPCC), particularly abuse cases; estimate its changes and compare it with trends in national consumption rates these drugs. We also aimed main characteristics population investigate major clinical effects poisoned patients.This is a retrospective patients admitted NPCC for acute poisoning involving gabapentinoids from 1 May 2012 October 2022.There were 357 (95.5%)...
Carbamazepine is antiepileptic drug widely used for the treatment of epilepsy. Due to low therapeutic index carbamazepine there a need routine measuring its concentrations in biological fluids. The aim study was describe method concomitant determination serum and saliva.Separation from matrix achieved by reversed-phase chromatography on C18 column, with mobile phase methanol-water-acetic acid (65:34:1) at flow-rate 1.0 ml/min. Detection effected ultra-violet absorption 285 nm. total run time...
In a commonly accepted model, in response to stimuli, bacterial histidine kinases undergo conformational transition between an active and inactive form. Structural information on is limited. By using ion mobility-mass spectrometry (IM-MS), we demonstrate exchange two populations of kinase ExsG that are linked different levels activity. atypical signaling protein incorporates uncommon catalytic core at the C terminus preceded by N-terminal "receiver domain" normally associated with regulator...
Benzodiazepines are among the most frequently ingested drugs in self-poisonings. Elderly may be at greater risk compared with younger individuals due to impaired metabolism and increased sensitivity benzodiazepines. The aim of this study was assess toxicity benzodiazepines elderly attempted suicide.A retrospective consecutive presentations hospital after self-poisoning done. Collected data consisted patient's characteristics (age, gender), benzodiazepine its blood concentrations admission,...
AhpD, a protein with two cysteine residues, is required for physiological reduction of the Mycobacterium tuberculosis alkylhydroperoxidase AhpC. AhpD also has an activity its own. The AhpC/AhpD system provides critical antioxidant protection, particularly in absence catalase-peroxidase KatG, which suppressed most isoniazid-resistant strains. Based on crystal structure, we proposed recently catalytic mechanism involving proton relay Glu118 carboxylate group, via His137 and water molecule,...
The resistance of <i>Mycobacterium tuberculosis</i> to isoniazid is commonly linked inactivation a catalase-peroxidase, KatG, that converts its biologically active form. Loss KatG associated with elevated expression the alkylhydroperoxidases AhpC and AhpD. AhpD has no sequence identity or other proteins but alkylhydroperoxidase activity possibly additional physiological activities. activity, in absence provides an important antioxidant defense. We have determined <i>M. structure resolution...