A5051624167- Cancer Research and Treatments
- Amino Acid Enzymes and Metabolism
- Garlic and Onion Studies
- Enzyme Structure and Function
- Biopolymer Synthesis and Applications
- Biochemical and Molecular Research
- Folate and B Vitamins Research
- Fungal Plant Pathogen Control
- Polyamine Metabolism and Applications
- Synthesis and Characterization of Heterocyclic Compounds
- Metabolism and Genetic Disorders
- Biochemical Acid Research Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Phytase and its Applications
- Nephrotoxicity and Medicinal Plants
- Microbial Metabolic Engineering and Bioproduction
- Cassava research and cyanide
- Cancer-related Molecular Pathways
- Sulfur-Based Synthesis Techniques
- Clostridium difficile and Clostridium perfringens research
- Parasitic Infections and Diagnostics
- Microbial metabolism and enzyme function
- Toxin Mechanisms and Immunotoxins
- Phytochemical compounds biological activities
- Synthesis and biological activity
Engelhardt Institute of Molecular Biology
2016-2025
University of Zagreb
2006
University of York
2006
Russian Academy of Sciences
2003
University of Parma
2003
Diallyl thiosulfinate (allicin) effectively inhibits the growth of various microorganisms, including antibiotic-resistant strains, so it can be considered to a broad-spectrum antimicrobial compound. However, its instability in bloodstream hinders use as therapeutic agent. We have synthesized number allicin analogues, both natural and synthetic, evaluated vitro their properties against Staphylococcus aureus Candida albicans. The compounds were shown exhibited more pronounced antifungal...
Acute and subchronic toxicity of the pharmacological pair based on encapsulated Citrobacter freundii C115H methionine γ-lyase enzyme/prodrug (methiin) was studied in female ICR mice. The drug showed a weak/moderate dose-dependent hepatotoxic effect. Most changes liver morphology identified were insignificant or mild deviations from norm. Long-term use single therapeutic dose per mouse 1.5 U C. @ (PEG-P(Asp)70/PLL70)-PIC-some/2 mg methiin led to slight decrease weight animals without obvious...
The steady-state kinetic parameters of pyridoxal 5-phosphate-dependent recombinant methionine -lyase from three pathogenic bacteria, Clostridium tetani, sporogenes, and Porphyromonas gingivalis, were determined in - -elimination reactions. enzyme C. sporogenes is characterized by the highest catalytic efficiency reaction L-methionine. It was demonstrated that these sources exists as a tetramer. N-terminal poly-histidine fragment enzymes influences their activity facilitates aggregation...
The problem of resistance to antibiotics requires the development new classes broad-spectrum antimicrobial drugs. concept pro-drugs allows researchers look for approaches obtain effective drugs with improved pharmacokinetic and pharmacodynamic properties. Thiosulfinates, formed enzymatically from amino acid sulfoxides upon crushing cells genus Allium plants, are known as compounds. instability high reactivity thiosulfinates complicate their use individual We propose a pharmacologically...
Tyrosine phenol-lyase, a tetrameric pyridoxal 5'-phosphate dependent enzyme, catalyzes the reversible hydrolytic cleavage of l-tyrosine to phenol and ammonium pyruvate. Here we describe crystal structure Citrobacter freundii holoenzyme at 1.9 Å resolution. The reveals network protein interactions with cofactor, 5'-phosphate, details coordination catalytically important K+ ion. We also present apoenzyme 1.85 Both structures were determined using crystals grown pH 8.0, which is close maximal...
The interaction of Citrobacter freundii methionine γ-lyase (MGL) and the mutant form in which Cys115 is replaced by Ala (MGL C115A) with nonprotein amino acid (2R)-2-amino-3-[(S)-prop-2-enylsulfinyl]propanoic (alliin) was investigated. It found that MGL catalyzes β-elimination reaction alliin to 2-propenethiosulfinate (allicin), pyruvate ammonia. followed inactivation modification SH groups wild-type enzymes. Three-dimensional structures inactivated (iMGL wild type) a C115A were determined...
Abstract The exploitation of methionine‐depleting enzyme methionine γ‐lyase (MGL) is a promising strategy against specific cancer cells that are strongly dependent on methionine. To identify MGL from different sources with high catalytic activity and efficient anticancer action, we have expressed characterized Clostridium novyi compared its efficiency the previously studied Citrobacter freundii . purified recombinant exhibits k cat /K m for γ‐elimination reaction 2.4‐ 1.36‐fold higher than...
Abstract O ‐acetylhomoserine sulfhydrylase (OAHS) is a pyridoxal 5′‐phosphate‐dependent enzyme involved in microbial methionine biosynthesis. In this study, we report gene cloning, protein purification, and some biochemical characteristics of OAHS from Clostridioides difficile . The tetramer with molecular weight 185 kDa. It possesses high activity the reaction L‐homocysteine synthesis, comparable to reported activities OAHSes other sources. inhibited by metabolic end product L‐methionine....
Pyridoxal 5'-phosphate-dependent methionine γ-lyase (MGL) catalyzes the β-elimination reaction of S-alk(en)yl-l-cysteine sulfoxides to thiosulfinates, which possess antimicrobial activity. Partial inactivation enzyme in course occurs due oxidation active site cysteine 115 conserved bacterial MGLs. In this work, C115H mutant form Clostridium sporogenes MGL was prepared and steady-state kinetic parameters were determined. The substitution results an increase catalytic efficiency towards...
Methionine γ-lyase (MGL) is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes the γ-elimination reaction of L-methionine. The promising target for therapeutic intervention in some anaerobic pathogens and has attracted interest as potential cancer treatment. crystal structure MGL from Clostridium sporogenes been determined at 2.37 Å resolution. fold protein similar to those homologous enzymes Citrobacter freundii, Entamoeba histolytica, Pseudomonas putida Trichomonas vaginalis. A...
Candida albicans and non-albicans species are a common cause of human mucosal infections, as well bloodstream infections deep mycoses. The emergence resistance spp. to antifungal drugs used in practice requires the search for new antimycotics. present study unravels potential synthetic dialk(en)ylthiosulfinates comparison with an enzymatic situ methionine γ-lyase-based thiosulfinate generation system (TGS). kinetics TGS reaction, namely, γ-lyase-catalyzed β-elimination S-alk(en)yl-L-cysteine...
Methionine deprivation of cancer cells, which are deficient in methionine biosynthesis, has been envisioned as a therapeutic strategy to reduce cell viability. γ-lyase (MGL), an enzyme that degrades methionine, exploited selectively remove the amino acid from environment. In order increase MGL catalytic activity, we performed sequence and structure conservation analysis MGLs various microorganisms. Whereas most residues active site at dimer interface were found be conserved, located...
The purpose of this study was to determine the anticancer effect dipropyl thiosulfinate produced in situ by pharmacological pair: (1) conjugated with daidzein C115H methionine γ-lyase (EC 4.4.1.11, MGL-Dz) and (2) substrate, S-propyl-L-cysteine sulfoxide (propiin) against various solid tumor types vitro vivo. MTT test used calculate IC50 values for HT29, COLO205 HCT116 (colon cancer); Panc1 MIA-PaCa2 (pancreatic 22Rv1, DU-145 PC3 (prostate cancer). most promising colon cancer cells observed...
Tryptophan indole-lyase (Trpase) from Proteus vulgaris is a pyridoxal 5'-phosphate dependent enzyme that catalyzes the reversible hydrolytic cleavage of l-Trp to yield indole and ammonium pyruvate. Asp-133 His-458 are strictly conserved in all sequences Trpase, they located proposed substrate-binding region Trpase. These residues were mutated alanine probe their role substrate binding catalysis. D133A mutant Trpase has no measurable activity with as substrate, but still retains...
Lung disease caused by Pseudomonas aeruginosa is the leading reason for death in cystic fibrosis patients. Therapeutic efficacy of pharmacological pairs, naked/encapsulated mutant form Citrobacter freundii methionine γ-lyase and substrates, sulfoxides S-substituted l-cysteine, generating thiosulfinates, was evaluated on murine model experimental sepsis multidrug-resistant P. 203-2 strain. The pairs containing naked enzyme substrates did not have antibacterial activity. treatment mice with...