Triosephosphate isomerase deficiency: Effect of F240L mutation on enzyme structure

2020 ◽  
Vol 689 ◽  
pp. 108473
Author(s):  
Jorge Miguel Romero
Keyword(s):  
Triosephosphate Isomerase ◽  
Enzyme Structure

Structures of c-di-GMP/cGAMP degrading phosphodiesterase VcEAL: identification of a novel conformational switch and its implication

2019 ◽  
Vol 476 (21) ◽  
pp. 3333-3353 ◽  
Author(s):  
Malti Yadav ◽  
Kamalendu Pal ◽  
Udayaditya Sen
Keyword(s):  
Active Site ◽  
Metal Binding ◽  
Metal Ion ◽  
Triosephosphate Isomerase ◽  
Catalytic Mechanism ◽  
Degradation Mechanism ◽  
Structural Basis ◽  
Conserved Residues ◽  
Phosphodiester Bond ◽  
Cyclic Dinucleotides

Cyclic dinucleotides (CDNs) have emerged as the central molecules that aid bacteria to adapt and thrive in changing environmental conditions. Therefore, tight regulation of intracellular CDN concentration by counteracting the action of dinucleotide cyclases and phosphodiesterases (PDEs) is critical. Here, we demonstrate that a putative stand-alone EAL domain PDE from Vibrio cholerae (VcEAL) is capable to degrade both the second messenger c-di-GMP and hybrid 3′3′-cyclic GMP–AMP (cGAMP). To unveil their degradation mechanism, we have determined high-resolution crystal structures of VcEAL with Ca2+, c-di-GMP-Ca2+, 5′-pGpG-Ca2+ and cGAMP-Ca2+, the latter provides the first structural basis of cGAMP hydrolysis. Structural studies reveal a typical triosephosphate isomerase barrel-fold with substrate c-di-GMP/cGAMP bound in an extended conformation. Highly conserved residues specifically bind the guanine base of c-di-GMP/cGAMP in the G2 site while the semi-conserved nature of residues at the G1 site could act as a specificity determinant. Two metal ions, co-ordinated with six stubbornly conserved residues and two non-bridging scissile phosphate oxygens of c-di-GMP/cGAMP, activate a water molecule for an in-line attack on the phosphodiester bond, supporting two-metal ion-based catalytic mechanism. PDE activity and biofilm assays of several prudently designed mutants collectively demonstrate that VcEAL active site is charge and size optimized. Intriguingly, in VcEAL-5′-pGpG-Ca2+ structure, β5–α5 loop adopts a novel conformation that along with conserved E131 creates a new metal-binding site. This novel conformation along with several subtle changes in the active site designate VcEAL-5′-pGpG-Ca2+ structure quite different from other 5′-pGpG bound structures reported earlier.

Medical and Veterinary Importance of the Moonlighting Functions of Triosephosphate Isomerase

2019 ◽  
Vol 20 (4) ◽  
pp. 304-315 ◽  
Author(s):  
Mónica Rodríguez-Bolaños ◽  
Ruy Perez-Montfort
Keyword(s):  
Cell Cycle ◽  
Immune Response ◽  
Triosephosphate Isomerase ◽  
Dihydroxyacetone Phosphate ◽  
Canonical Function ◽  
Moonlighting Protein ◽  
Veterinary Importance ◽  
Moonlighting Functions

Triosephosphate isomerase is the fifth enzyme in glycolysis and its canonical function is the reversible isomerization of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Within the last decade multiple other functions, that may not necessarily always involve catalysis, have been described. These include variations in the degree of its expression in many types of cancer and participation in the regulation of the cell cycle. Triosephosphate isomerase may function as an auto-antigen and in the evasion of the immune response, as a factor of virulence of some organisms, and also as an important allergen, mainly in a variety of seafoods. It is an important factor to consider in the cryopreservation of semen and seems to play a major role in some aspects of the development of Alzheimer's disease. It also seems to be responsible for neurodegenerative alterations in a few cases of human triosephosphate isomerase deficiency. Thus, triosephosphate isomerase is an excellent example of a moonlighting protein.

scholarly journals Exoproteome Perspective on the Bile Stress Response of Lactobacillus johnsonii

Proteomes ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 10
Author(s):  
Bernadette B. Bagon ◽  
Valerie Diane V. Valeriano ◽  
Ju Kyoung Oh ◽  
Edward Alain B. Pajarillo ◽  
Ji Yoon Lee ◽  
...  
Keyword(s):  
Cell Wall ◽  
Stress Response ◽  
Triosephosphate Isomerase ◽  
Extracellular Proteins ◽  
Metabolic Adaptation ◽  
Gi Tract ◽  
Phosphotransferase System ◽  
Lactobacillus Johnsonii ◽  
Promoting Effect ◽  
Leading Role

Probiotics must not only exert a health-promoting effect but also be capable of adapting to the harsh environment of the gastrointestinal (GI) tract. Probiotics in the GI tract must survive the cell wall-disrupting effect of bile acids. We investigated the exoproteome of Lactobacillus johnsonii PF01 and C1-10 under bile stress. A comparative analysis revealed the similarities between the two L. johnsonii exoproteomes, as well as their different responses to bile. The large number of metabolic proteins in L. johnsonii revealed its metabolic adaptation to meet protein synthesis requirements under bile stress. In addition, cell wall modifications occurred in response to bile. Furthermore, some extracellular proteins of L. johnsonii may have moonlighting function in the presence of bile. Enolase, L-lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, triosephosphate isomerase, 50s ribosomal protein L7/L12, and cellobiose-specific phosphotransferase system (PTS) sugar transporter were significantly upregulated under bile stress, suggesting a leading role in the collective bile stress response of L. johnsonii from its exoproteome perspective.

scholarly journals Sparse Evidence for Giardia intestinalis, Cryptosporidium spp. and Microsporidia Infections in Humans, Domesticated Animals and Wild Nonhuman Primates Sharing a Farm–Forest Mosaic Landscape in Western Uganda

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 933
Author(s):  
Marie Cibot ◽  
Matthew R. McLennan ◽  
Martin Kváč ◽  
Bohumil Sak ◽  
Caroline Asiimwe ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Triosephosphate Isomerase ◽  
Ribosomal Subunit ◽  
Oral Route ◽  
Pathogen Transmission ◽  
Mosaic Landscape ◽  
Domesticated Animals ◽  
Black And White ◽  
Cryptosporidium Spp ◽  
Animal Contact

Zoonotic pathogen transmission is considered a leading threat to the survival of non-human primates and public health in shared landscapes. Giardia spp., Cryptosporidium spp. and Microsporidia are unicellular parasites spread by the fecal-oral route by environmentally resistant stages and can infect humans, livestock, and wildlife including non-human primates. Using immunoassay diagnostic kits and amplification/sequencing of the region of the triosephosphate isomerase, small ribosomal subunit rRNA and the internal transcribed spacer genes, we investigated Giardia, Cryptosporidium, and microsporidia infections, respectively, among humans, domesticated animals (livestock, poultry, and dogs), and wild nonhuman primates (eastern chimpanzees and black and white colobus monkeys) in Bulindi, Uganda, an area of remarkably high human–animal contact and spatial overlap. We analyzed 137 fecal samples and revealed the presence of G. intestinalis assemblage B in two human isolates, G. intestinalis assemblage E in one cow isolate, and Encephalitozoon cuniculi genotype II in two humans and one goat isolate. None of the chimpanzee and colobus monkey samples were positive for any of the screened parasites. Regular distribution of antiparasitic treatment in both humans and domestic animals in Bulindi could have reduced the occurrence of the screened parasites and decreased potential circulation of these pathogens among host species.

scholarly journals Multilocus Genotyping of Giardia duodenalis in Mostly Asymptomatic Indigenous People from the Tapirapé Tribe, Brazilian Amazon

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 206
Author(s):  
Pamela Carolina Köster ◽  
Antonio F. Malheiros ◽  
Jeffrey J. Shaw ◽  
Sooria Balasegaram ◽  
Alexander Prendergast ◽  
...  
Keyword(s):  
Triosephosphate Isomerase ◽  
Gastrointestinal Symptoms ◽  
Giardia Duodenalis ◽  
Protozoan Parasite ◽  
Indigenous Communities ◽  
Brazilian Amazon ◽  
Epidemiological Survey ◽  
Small Subunit ◽  
High Genetic Diversity ◽  
Cross Sectional

Little information is available on the occurrence and genetic variability of the diarrhoea-causing enteric protozoan parasite Giardia duodenalis in indigenous communities in Brazil. This cross-sectional epidemiological survey describes the frequency, genotypes, and risk associations for this pathogen in Tapirapé people (Brazilian Amazon) at four sampling campaigns during 2008–2009. Microscopy was used as a screening test, and molecular (PCR and Sanger sequencing) assays targeting the small subunit ribosomal RNA, the glutamate dehydrogenase, the beta-giardin, and the triosephosphate isomerase genes as confirmatory/genotyping methods. Associations between G. duodenalis and sociodemographic and clinical variables were investigated using Chi-squared test and univariable/multivariable logistic regression models. Overall, 574 individuals belonging to six tribes participated in the study, with G. duodenalis prevalence rates varying from 13.5–21.7%. The infection was positively linked to younger age and tribe. Infected children <15 years old reported more frequent gastrointestinal symptoms compared to adults. Assemblage B accounted for three out of four G. duodenalis infections and showed a high genetic diversity. No association between assemblage and age or occurrence of diarrhoea was demonstrated. These data indicate that the most likely source of infection was anthropic and that different pathways (e.g., drinking water) may be involved in the transmission of the parasite.

The Relationship of the −5, −8, and −24 Variant Alleles in African Americans to Triosephosphate Isomerase (TPI) Enzyme Activity and to TPI Deficiency

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2959-2962 ◽  
Author(s):  
Arthur Schneider ◽  
Linda Forman ◽  
Beryl Westwood ◽  
Catherine Yim ◽  
James Lin ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
African American ◽  
African Americans ◽  
Triosephosphate Isomerase ◽  
Small Subset ◽  
Nucleotide Substitutions ◽  
Severe Deficiency ◽  
American Society ◽  
Relationship Of ◽  
The Relationship

Abstract In 424 African-American and 75 white subjects, we found that the −5 (TPI 592 A→G), −8 (TPI 589 G→A), and −24 (TPI 573 T→G) variants in the triosephosphate isomerase (TPI) gene occurred frequently (41.0%) in the African-American subjects but did not occur in the whites. These data suggest that this set of polymorphisms may turn out to be one of the higher-incidence molecular markers of African lineage, a surprising finding because others had reported that these nucleotide substitutions were restricted to a small subset of African Americans who had been characterized as TPI-deficiency heterozygotes. Additionally, we investigated the relationship of these variants to TPI-enzyme activity. Although the variant substitutions (occurring in three haplotypes: −5 alone, −5 −8, and −5 −8 −24) were associated with moderate reduction in enzyme activity, severe-deficiency heterozygotes could not be identified with certainty, and none of the haplotypes were restricted to subjects with marked reduction of enzyme activity. Three subjects were homozygous for the −5 −8 haplotype, a finding inconsistent with the putative role of this haplotype as the cause of a null variant incompatible with life in homozygotes. Despite these findings, the possibility remains that the −5 −8 or −5 −8 −24 haplotypes may in some instances contribute to compound heterozygosity and clinical TPI deficiency. © 1998 by The American Society of Hematology.

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