- Erythrocyte Function and Pathophysiology
- Trypanosoma species research and implications
- Biochemical and Molecular Research
- Research on Leishmaniasis Studies
- Enzyme Structure and Function
- Amoebic Infections and Treatments
- Pancreatic function and diabetes
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Neonatal Health and Biochemistry
- Parasitic Infections and Diagnostics
- Pancreatitis Pathology and Treatment
- Glycosylation and Glycoproteins Research
- Toxin Mechanisms and Immunotoxins
- Calcium signaling and nucleotide metabolism
- Proteins in Food Systems
- Diagnosis and treatment of tuberculosis
- Advanced Glycation End Products research
- Vector-borne infectious diseases
- Protease and Inhibitor Mechanisms
- Biomedical Research and Pathophysiology
- Eosinophilic Disorders and Syndromes
- Protein Hydrolysis and Bioactive Peptides
- Hemoglobin structure and function
- S100 Proteins and Annexins
Universidad Nacional Autónoma de México
2013-2023
Google (United States)
2016
Instituto Nacional de Pediatria
2001-2008
Universitat de Barcelona
2006
Universidad Autónoma Metropolitana
1994-2004
Instituto Nacional de Cardiología
1989-2002
Tribunal Electoral del Estado de México
1997
National Institutes of Health
1982-1984
National Institute of Arthritis and Musculoskeletal and Skin Diseases
1982-1984
Human triosephosphate isomerase deficiency is a rare autosomal disease that causes premature death of homozygous individuals. The most frequent mutation leads to this illness in position 104, which involves conservative change Glu for Asp. Despite the extensive work has been carried out on E104D mutant enzyme hemolysates and whole cells, molecular basis poorly understood. Here, we show purified, recombinant E104D, while exhibiting normal catalytic activity, shows impairments formation active...
Our laboratory previously found that under conditions stabilized the interaction between alpha and beta subunits of receptor for immunoglobulin E, two new components were recovered having apparent molecular weights 45 000 20 000, respectively. In this paper, we characterize 20-kDa material. We demonstrate it consists a disulfide-linked dimer 10-kDa polypeptides these have all characteristics expected receptor. propose they be termed gamma chains four chains: one alpha, beta, chains. The...
We examined the interfaces of homodimeric triosephosphate isomerase (TIM) from eight different species. The crystal structures enzymes showed that a portion interface is markedly similar in TIMs Trypanosoma cruzi (TcTIM), brucei, and Leishmania mexicana significantly human, yeast, chicken, Plasmodium falciparum, Entamoeba histolytica. Since this interfacial region central stability TcTIM, we hypothesized it would be possible to find agents selectively affect three trypanosomatids. found...
Background Chagas disease affects around 18 million people in the American continent. Unfortunately, there is no satisfactory treatment for disease. The drugs currently used are not specific and exert serious toxic effects. Thus, an urgent need that effective. Looking molecules to eliminate parasite, we have targeted a central enzyme of glycolytic pathway: triosephosphate isomerase (TIM). homodimeric catalytically active only as dimer. Because significant differences interface enzymes from...
Abstract Triosephosphate isomerase (TIM) is an essential Trypanosoma cruzi enzyme and one of the few validated drug targets for Chagas disease. The known inhibitors this behave poorly or have low activity in parasite. In work, we used symmetrical diarylideneketones derived from structures with trypanosomicidal activity. We obtained enzymatic inhibitor IC 50 value 86 n m without inhibition effects on mammalian enzyme. These molecules also affected cruzipain, another proteolytic This dual...
In triosephosphate isomerase, Cys126 is a conserved residue located close to the catalytic glutamate, Glu165. Although it has been mentioned that and other nearby residues are required maintain active site geometry optimal for catalysis, no evidence supporting this idea reported date. work, we studied stability properties of mutants C126A C126S Saccharomyces cerevisiae TIM (wtTIM). None these amino acid replacements induced significant changes in folding wtTIM, as indicated by spectroscopic...
For more than 50 years, it has been known that K+ is an essential activator of pyruvate kinase (Kachmar, J. F., and Boyer, P. D. (1953) Biol. Chem. 200, 669-683). However, the role in catalysis by not totally understood. Previous studies without showed affinity ADP-Mg2+ depends on concentration phosphoenolpyruvate, although kinetics enzyme at saturating concentrations show independence binding substrates (Reynard, A. M., Hass, L. Jacobsen, & (1961) 236, 2277-2283). Here, we explored with K+....
The amino acid sequence of triosephosphate isomerase from Trypanosoma brucei , cruzi and Leishmania mexicana have an identity 68 %. Using the numbering system for T. enzyme, in their aligned sequences, leishmanial enzymes cysteine residues at positions 14, 40, 117 126. has 40 126, a valine residue position 117. Dithionitrobenzoic methylmethane thiosulfonate inhibited three enzymes, but was more than 100‐fold sensitive. sensitivity wild type to reagents equal that Cys117Val Val117Cys mutant...
Homodimeric triosephosphate isomerases from Trypanosoma cruzi (TcTIM) and brucei (TbTIM) have markedly similar catalytic properties 3-D structures; their overall amino acid sequence identity is 68% 85% in interface residues. Nonetheless, active dimer formation guanidinium chloride unfolded monomers faster more efficient TcTIM than TbTIM. The enzymes thus provide a unique opportunity for exploring the factors that control of dimers. kinetics reactivation at different protein concentrations...
A series of fifty arylideneketones and thiazolidenehydrazines was evaluated against Leishmania infantum braziliensis. Furthermore, new simplified thiazolidenehydrazine derivatives were Trypanosoma cruzi. The cytotoxicity the active compounds on non-infected fibroblasts or macrophages established in vitro to evaluate selectivity their anti-parasitic effects. Seven ten had good activity three parasites. IC50 values for T. cruzi spp. ranged from 90 nM-25 µM. Eight multi-trypanocidal (the...
The gene that encodes for triosephosphate isomerase from Trypanosoma cruzi was cloned and sequenced. In T. cruzi, there is only one isomerase. enzyme has an identity of 72% 68% with brucei Leishmania mexicana, respectively. active site residues are conserved: out the 32 conform interface dimeric brucei, 29 conserved in enzyme. expressed Escherichia coli purified to homogeneity. Data electrophoretic analysis under denaturing techniques filtration showed a homodimer. Some its structural...
We describe experiments which indicate that lipids interact with the receptor for immunoglobulin E (IgE) in several ways. Evidence loosely bound lipid comes from observations on special conditions are required order to oxidatively iodinate alpha chain of IgE-receptor complexes. tightly, but still noncovalently, studies inhibit dissociation subunits micellar detergent. Finally, biosynthetic contain ester-linked fatty acids. The latter modification appears take place receptors have already...