A5075154850- Biochemical and Molecular Research
- Tuberculosis Research and Epidemiology
- Enzyme Structure and Function
- Microbial Natural Products and Biosynthesis
- Mycobacterium research and diagnosis
- Microbial Metabolic Engineering and Bioproduction
- HIV/AIDS drug development and treatment
- Enzyme Catalysis and Immobilization
- Carbohydrate Chemistry and Synthesis
- Biofuel production and bioconversion
- Bacterial Genetics and Biotechnology
- Microbial Metabolites in Food Biotechnology
- Cancer therapeutics and mechanisms
- Enzyme Production and Characterization
- Metabolomics and Mass Spectrometry Studies
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Selenium in Biological Systems
- Chemical Reactions and Isotopes
- Antibiotic Resistance in Bacteria
- Synthesis and biological activity
- Computational Drug Discovery Methods
- Neurological diseases and metabolism
- Cytomegalovirus and herpesvirus research
- Pneumocystis jirovecii pneumonia detection and treatment
Universidade de São Paulo
2015-2025
WiLAN (Canada)
2024
University of Warwick
2019-2023
Universidade Estadual Paulista (Unesp)
2003-2023
University of Cambridge
2009-2023
Institute of Biomedical Science
2020-2023
Universidade Estadual de Campinas (UNICAMP)
2018-2020
Instituto Butantan
2018
Laboratório Nacional de Ciência e Tecnologia do Bioetanol
2013-2017
Brazilian Biosciences National Laboratory
2013-2017
Abstract Tetrahydropyran rings are a common feature of complex polyketide natural products, but much remains to be learned about the enzymology their formation. The enzyme SalBIII from salinomycin biosynthetic pathway resembles other polyether epoxide hydrolases/cyclases MonB family, plays no role in conventional cascade ring opening/closing. Mutation salBIII gene gave metabolite which A is not formed. Using this vitro as substrate analogue, has been shown form pyran A. We have determined...
Tuberculosis made a resurgence in the mid-1980s and now kills approximately 3 million people year. The re-emergence of tuberculosis as public health threat, high susceptibility HIV-infected persons proliferation multi-drug-resistant strains have created need to develop new drugs. Shikimate kinase other enzymes shikimate pathway are attractive targets for development non-toxic antimicrobial agents, herbicides anti-parasitic drugs, because is essential these species whereas it absent from...
Genetically antimicrobial resistance in Mycobacterium tuberculosis is currently one of the most important aspects tuberculosis, considering that there are emerging resistant strains for almost every known drug used its treatment. There multiple antimicrobials treatment, and effective ones first-line drugs, which include isoniazid, pyrazinamide, rifampicin, ethambutol. In this context, understanding mechanisms action these molecules essential proposing new therapies strategies Additionally,...
The coenzyme A (CoA) biosynthesis pathway has attracted attention as a potential target for much-needed novel antimicrobial drugs, including the treatment of tuberculosis (TB), lethal disease caused by Mycobacterium (Mtb). Seeking to identify inhibitors Mtb phosphopantetheine adenylyltransferase (MtbPPAT), enzyme that catalyses penultimate step in CoA biosynthesis, we performed fragment screen. In doing so, discovered three series fragments occupy distinct regions MtbPPAT active site,...
The shikimate pathway is essential in Mycobacterium tuberculosis and its absence from humans makes the enzymes of this potential drug targets. In present paper, we provide structural insights into ligand inhibitor binding to 3-dehydroquinate dehydratase (dehydroquinase) M. (MtDHQase), third enzyme pathway. has been crystallized complex with reaction product, 3-dehydroshikimate, six different competitive inhibitors. 2,3-anhydroquinate mimics flattened enol/enolate intermediate serves as an...
Bacteria, fungi and plants can convert carbohydrate phosphoenolpyruvate into chorismate, which is the precursor of various aromatic compounds. The seven enzymes shikimate pathway are responsible for this conversion. Shikimate kinase (SK) fifth enzyme in converts to shikimate-3-phosphate. In work, conformational changes that occur on binding shikimate, magnesium chloride ions SK from Mycobacterium tuberculosis (MtSK) described. It was observed both influence conformation residues active site...
Gentamicins are heavily methylated, clinically valuable pseudotrisaccharide antibiotics produced by Micromonospora echinospora. GenN has been characterized as an S-adenosyl-l-methionine-dependent methyltransferase with low sequence similarity to other enzymes. It is responsible for the 3″-N-methylation of 3″-dehydro-3″-amino-gentamicin A2, essential modification ring III in biosynthetic pathway gentamicin C complex. Purified recombinant also efficiently catalyzes related aminoglycosides...
The thioesterase FlK from the fluoroacetate-producing Streptomyces cattleya catalyzes hydrolysis of fluoroacetyl-coenzyme A. This provides an effective self-defense mechanism, preventing any A formed being further metabolized to 4-hydroxy-trans-aconitate, a lethal inhibitor tricarboxylic acid cycle. Remarkably, does not accept acetyl-coenzyme as substrate. Crystal structure analysis shows that forms dimer, in which each subunit adopts hot dog fold observed for type II thioesterases. Unlike...
Gentamicins are clinically relevant aminoglycoside antibiotics produced by several Micromonospora species. highly methylated and functionalized molecules, their biosynthesis include glycosyltransferases, dehydratase/oxidoreductases, aminotransferases, methyltransferases. The of gentamicin A from A2 involves three enzymatic steps that modify the hydroxyl group at position 3″ unusual garosamine sugar to provide its substitution for an amino group, followed N-methylation. first these reactions...
Dihydrofolate reductase (DHFR), a key enzyme involved in folate metabolism, is widely explored target the treatment of cancer, immune diseases, bacteria, and protozoa infections. Although several antifolates have proved successful infectious they been underexplored to combat tuberculosis, despite essentiality M. tuberculosis DHFR (MtDHFR). Herein, we describe an integrated fragment-based drug discovery approach MtDHFR that has identified hits with scaffolds not yet any previous design...
Abstract Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia. The oxygen-dependent stability and activity of the HIF-α subunits is traditionally associated post-translational modifications such as hydroxylation, acetylation, ubiquitination phosphorylation. Here we report novel evidence showing unsaturated fatty acids are naturally occurring, non-covalent structural ligands HIF-3α, thus providing initial framework for exploring its...