Disease relevance of ECs4844

• The purification and characterization of triose-phosphate isomerase from the psychrophilic bacterium Vibrio marinus (vTIM) is described [1].
• The urea-induced unfolding of the alpha subunit of tryptophan synthase (alphaTS) from Escherichia coli, an eight-stranded (beta/alpha)(8) TIM barrel protein, has been shown to involve two stable equilibrium intermediates, I1 and I2, well populated at approximately 3 M and 5 M urea, respectively [2].
• The role of native contact topology in the folding of a TIM barrel model based on the alpha-subunit of tryptophan synthase (alphaTS) from Salmonella typhimurium (Protein Data Bank structure 1BKS) was studied using both equilibrium and kinetic simulations [3].
• By analysis of genomic clones, we have determined the complete nucleotide sequence of the gene encoding triosephosphate isomerase (TIM; EC 5.3.1.1) in the thermophilic bacterium, Bacillus stearothermophilus [4].
• The enzyme has a highly conserved catalytic TIM-barrel region as previously described for Serratia marcescens ChiA [5].

High impact information on ECs4844

• To address this question, the gene encoding a sluggish mutant triose-phosphate isomerase (D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1) has been subjected to random mutagenesis over its whole length by using "spiked" oligonucleotide primers [6].
• Amino acid sequence comparison reveals that vTIM has an alanine in loop 8 (at position 238), whereas all other TIM sequences known to date have a serine [1].
• An obligatory intermediate controls the folding of the alpha-subunit of tryptophan synthase, a TIM barrel protein [7].
• Both dihydroorotases are members of the metallo-dependent hydrolase superfamily, whose members have a distorted "TIM barrel" domain containing the active site [8].
• This structure reveals an octameric particle of 422 symmetry, with each polypeptide chain organized in a (alphabeta)(8) TIM-like barrel catalytic domain attached to a U-shaped beta-sandwich domain [9].

Chemical compound and disease context of ECs4844

• Apparent radii of the native, stable intermediates and unfolded conformers of the alpha-subunit of tryptophan synthase from E. coli, a TIM barrel protein [10].
• This is consistent with the hypothesis that PV4-8 TPI increased arsenate resistance in E. coli by directly or indirectly functioning as an arsenate reductase [11].
• In this study, a tpi1 gene encoding for the enzyme triose phosphate isomerase in Klebsiella pneumoniae DSM2026 was knocked out in an effort to metabolically engineer this strain as a model system for the production of 1,3-propanediol [12].
• In this study, the antimicrobial activity of ticarcillin-clavulonic acid (TIM) was investigated by the minimal inhibitory concentration (MIC) method on strains of Aeromonas, Citrobacter, Hafnia, Morganella, Proteus, Pseudomonas and gram negative bacteria isolated from raw milk [13].

Biological context of ECs4844

• These genes are clustered, suggesting an operon organization, and they are immediately followed by the putative gene for the triose phosphate isomerase, an enzyme used during glycolysis [14].

Associations of ECs4844 with chemical compounds

• Proline replacements and the simplification of the complex, parallel channel folding mechanism for the alpha subunit of Trp synthase, a TIM barrel protein [15].
• Paradoxically, P. vittata TPI activity was not more resistant to inhibition by arsenate in vitro than its bacterial counterpart suggesting that arsenate resistance of conventional TPI reaction was not the basis for the cellular arsenate resistance [11].
• Deletion mutagenesis as a test of evolutionary relatedness of indoleglycerol phosphate synthase with other TIM barrel enzymes [16].
• P. vittata TPI activity was inhibited by incubation with reduced glutathione while bacterial TPI was unaffected [11].
• We have predicted mutations that introduce triose phosphate isomerase activity into ribose-binding protein, a receptor that normally lacks enzyme activity [17].

Other interactions of ECs4844

• The triose phosphate isomerase and enolase from B. subtilis are extremely similar to those from all other species, both eukaryotic and prokaryotic [18].
• For example, the enzymes superoxide dismutase, triose-phosphate isomerase, and acetylcholinesterase can steer ligands toward their oppositely charged binding pockets or gorges [19].

Analytical, diagnostic and therapeutic context of ECs4844

• The high representation of the TIM barrel as a scaffold for enzymatic proteins makes it an interesting model for protein engineering [20].

References