Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structure of holo-glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus has been crystallographically refined at 1.8 A resolution using restrained least-squares refinement methods. The final crystallographic R-factor for 93,120 reflexions with F greater than 3 sigma (F) is 0.177. The asymmetric unit of the crystal contains a complete tetramer, the final model of which incorporates a total of 10,272 unique protein and coenzyme atoms together with 677 bound solvent molecules. The structure has been analysed with respect to molecular symmetry, intersubunit contacts, coenzyme binding and active site geometry. The refined model shows the four independent subunits to be remarkable similar apart from local deviations due to intermolecular contacts within the crystal lattice. A number of features are revealed that had previously been misinterpreted from an earlier 2.7 A electron density map. Arginine at position 195 (previously thought to be a glycine) contributes to the formation of the anion binding sites in the active site pocket, which are involved in binding of the substrate and inorganic phosphates during catalysis. This residue seems to be structurally equivalent to the conserved Arg194 in the enzyme from other sources. In the crystal both of the anion binding sites are occupied by sulphate ions. The ND atom of the catalytically important His176 is hydrogen-bonded to the main-chain carbonyl oxygen of Ser177, thus fixing the plane of the histidine imidazole ring and preventing rotation. The analysis has revealed the presence of several internal salt-bridges stabilizing the tertiary and quaternary structure. A significant number of buried water molecules have been found that play an important role in the structural integrity of the molecule.
J Mol Biol 1987 Jan 05
PMID:Structure of holo-glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus at 1.8 A resolution. 358 18

The interaction of glyceraldehyde 3-phosphate dehydrogenase with microtubules has been studied by measurement of the amount of enzyme which co-assembles with in vitro reconstituted microtubules. The binding of glyceraldehyde 3-phosphate dehydrogenase to microtubules is a saturable process; the maximum binding capacity is about 0.1 mole of enzyme bound per mole of assembled tubulin. Half saturation of microtubule binding sites is obtained at a concentration of glyceraldehyde 3-phosphate dehydrogenase of about 0.5 microM. Glyceraldehyde 3-phosphate dehydrogenase (between 0.1 and 2 microM) induces a concentration-dependent increase a) in the turbidity of the microtubule suspension without alteration of the net amount of polymer formed and b) in the amount of microtubule protein polymers after cold microtubule disassembly. There is a linear relationship between the intensity of the glyceraldehyde 3-phosphate dehydrogenase-induced effects and the amount of microtubule-bound enzyme. The specificity of the association of glyceraldehyde 3-phosphate dehydrogenase to microtubules has been documented by copolymerization experiments. Assembly-disassembly cycles of purified microtubules in the presence of a crude liver soluble fraction results in the selective extraction of a protein with an apparent molecular weight of 35,000 identified as the monomer of glyceraldehyde 3-phosphate dehydrogenase by peptide mapping and immunoblotting. In conclusion, microtubules possess a limited number of binding sites for glyceraldehyde 3-phosphate dehydrogenase. The binding of the glycolytic enzyme to microtubules shows a considerable specificity and is associated with alterations of assembly and disassembly characteristics of microtubules.
Mol Cell Biochem 1987 Mar
PMID:Binding of glyceraldehyde 3-phosphate dehydrogenase to microtubules. 358 30

Ablation of premigratory trunk neural crest over somites 10 through 20 gives rise to chick hearts which lack sympathetic innervation. Norepinephrine, the neurotransmitter of the postganglionic sympathetic nerves, increases the rate of formation of cyclic AMP (cAMP) in cells. Cyclic AMP the modulator of certain key enzymes of metabolism, was decreased in sympathetically-aneural hearts. Six histochemical assays were used to investigate the metabolic profile of sympathetically aneural hearts as compared to control hearts. NADH-tetrazolium reductase activity (indicator of oxidative metabolism), glyceraldehyde 3-phosphate dehydrogenase activity (indicator of glycolytic rate), beta-hydroxybutyrate dehydrogenase (indicator of beta-oxidation of fatty acids), and oil red 0 assay (neutral lipid content) each demonstrated no difference between aneural and control hearts. Periodic acid-Schiff method for glycogen content, indicated greater stores of glycogen in aneural hearts compared to controls. alpha-Glucan phosphorylase, an enzyme responsible for glycogen hydrolysis, showed less activity in aneural hearts than in controls. The results indicate that the sympathetically aneural heart's metabolism is altered by decreased capability in the maximal rate of glycogen breakdown (decreased phosphorylase Vmax) and subsequent increased storage of the glycogen substrate. Enzymes of other energy transformation pathways were unaltered in the absence of sympathetic nerves.
J Mol Cell Cardiol 1987 Apr
PMID:Carbohydrate, lipid and oxidative metabolism in the sympathetically aneural chick heart. 361 18

Crystals of glyceraldehyde phosphate dehydrogenase from the glycosome of Trypanosoma brucei brucei have been grown, and a partial data set has been collected using synchrotron radiation. The crystals diffract initially to 2.3 A resolution. The space group is P2(1)2(1)2, with cell dimensions a = 135 A, b = 255 A, c = 115 A, so there are probably at least two tetramers in the asymmetric unit.
J Mol Biol 1987 Apr 05
PMID:Preliminary crystallographic studies of glycosomal glyceraldehyde phosphate dehydrogenase from Trypanosoma brucei brucei. 362 77

Cytoplasmic beta-actin and five glycolytic enzyme cDNAs were isolated from a rat skeletal muscle cDNA library and together with a genomic clone of rat cytochrome c were used as probes to quantitate the respective RNA transcription rates in isolated nuclei run off transcription assays from stationary cells cultured under normal or 2% oxygen. The transcription rates of lactate dehydrogenase, pyruvate kinase, triosephosphate isomerase and aldolase increased by 2-5 fold during the 72 hr exposure to 2% oxygen. There was a small increase in actin RNA transcription while both cytochrome c and glyceraldehyde-3-phosphate dehydrogenase RNA transcription rates decreased. Since previous studies demonstrated an increase in steady state glyceraldehyde-3-phosphate dehydrogenase RNA during low O2 exposure it is concluded that the level of this RNA is regulated post transcriptionally whereas the other four glycolytic enzyme RNAs are regulated at least partially at the level of transcription by oxygen availability. The relative transcriptional rates of the RNAs in this study are related to their cellular RNA and protein concentrations.
Mol Cell Biochem 1987 Sep
PMID:Regulation of glycolytic enzyme RNA transcriptional rates by oxygen availability in skeletal muscle cells. 369 61

Pentalenolactone (PL), an antibiotic produced by several strains of Streptomycetes, is a specific irreversible inhibitor of glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12). The effect of this antibiotic was studied in Trypanosoma brucei. In infected mice, due to the rapid metabolic inactivation of PL in vivo, trypanosomes were not affected by concentrations that were lethal to the host. Bloodstream trypanosomes in vitro were killed by low concentrations of PL (1.5 microgram ml-1), suggesting that there is no alternative to the glycolytic pathway for the generation of ATP in the bloodstream forms. In contrast, even high concentrations of PL (75 micrograms ml-1) were unable to inhibit growth of the procyclic form in vitro, presumably due to their ability to generate ATP independently of the glycolytic pathway.
Mol Biochem Parasitol 1986 Jun
PMID:Inhibition of glyceraldehyde-3-phosphate dehydrogenase by pentalenolactone in Trypanosoma brucei. 373 93

The glycosomes of in vitro grown procyclic trypomastigote forms of Trypanosoma brucei were purified by three different procedures and the results compared by electron microscopy, enzyme assays and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Centrifugation on a self-forming Percoll gradient followed by a sucrose gradient centrifugation resulted in the least enriched glycosomal preparation. Centrifugation on a pre-formed Nycodenz gradient gave an improved preparation but the most homogeneous preparation of intact glycosomes was obtained after centrifugation on two successive sucrose gradients. Glycosomes purified by both the Nycodenz and double sucrose gradient procedures appeared larger than in situ glycosomes presumably due to an osmotic effect resulting from disruption of the granular matrix of the organelles. Nevertheless, there appears to be no loss of cisternal contents due to the swelling of the organelles. The glycosomes of the bloodstream form trypomastigotes purified by the same procedures show, however, no sign of swelling. A comparison of glycosomes purified from procyclic trypomastigotes and bloodstream form trypomastigotes prepared by the same double sucrose procedure demonstrated that in the glycosome of procyclic trypomastigotes: activities of hexokinase, phosphoglucose isomerase, phosphofructose kinase, aldolase and phosphoglycerate kinase and diminished by 80-100%; activities of glyceraldehyde-3-phosphate dehydrogenase, triose phosphate isomerase and glycerol-3-phosphate dehydrogenase remain unchanged or are only slightly reduced; there is an appearance of four major new proteins, among which could be phosphoenol pyruvate carboxykinase and malate dehydrogenase. These observations are in basic agreement with those by Hart et al. (Mol. Biochem. Parasitol. 12, 25-35, 1984).
Mol Biochem Parasitol 1986 Dec
PMID:An improved purification of glycosomes from the procyclic trypomastigotes of Trypanosoma brucei. 380 43

Analysis of human glyceraldehyde-3-phosphate dehydrogenase mRNA revealed that levels in adult skeletal muscle are 12-fold greater per microgram of polyadenylated RNA than in fetal skeletal muscle, whereas in cardiac muscle RNA levels were about equal in fetal and adult tissue. The mRNA levels correlate well with glyceraldehyde 3-phosphate dehydrogenase enzyme activities. There was no evidence for fetus- or tissue-specific forms.
Mol Cell Biol 1985 Aug
PMID:Human glyceraldehyde-3-phosphate dehydrogenase: mRNA levels and enzyme activity in developing muscle. 383 56

The ploidy of trypanosomes has until now remained undetermined, although isoenzyme studies and direct measurements of DNA content and complexity suggest diploidy. Direct cytogenetic analysis is not possible, because the chromosomes do not condense at any stage of the cell cycle. We now present evidence from analysis of restriction site polymorphisms in and around three glycolytic enzyme genes (phosphoglycerate kinase, triosephosphate isomerase, glyceraldehyde phosphate dehydrogenase) and the tubulin gene cluster, that trypanosomes of subgenus Trypanozoon are diploid for these housekeeping genes. This result is still compatible with the single copy nature of variant surface glycoprotein (VSG) genes in Trypanozoon, if different VSG genes are present in corresponding positions on paired chromosomes. Using pulse field gradient gel electrophoresis, we show that the genes for the three glycolytic enzymes are all located in very large DNA molecules, but the gene for triosephosphate isomerase is in another fraction from the genes for the other two enzymes. Since all three enzymes are located in glycosomes, which are trypanosome microbodies, the genes for glycosomal enzymes are not all clustered in one chromosomal segment of the trypanosome genome.
Mol Biochem Parasitol 1985 Sep
PMID:Trypanosomes of subgenus Trypanozoon are diploid for housekeeping genes. 384 May 71

We have compared the molecular karyotypes of trypanosomes from different subgroups within subgenus Trypanozoon by pulsed field gradient (PFG) gel electrophoresis. Although the overall karyotype was similar, there was much variation in the size of chromosomes between different stocks. Two of three stocks of Trypanosoma (Trypanozoon) brucei gambiense had remarkably small mini-chromosomes: 25-50 kilobase pairs compared to 50-150 kilobase pairs for the mini-chromosomes of other Trypanozoon stocks. The relative amount of DNA in the mini-chromosomal fraction of different stocks correlated well with the amount of 177 base pair satellite DNA monomer per microgram nuclear DNA. Hybridisation of Southern blots of pulsed field gradient gels with a number of gene probes showed that the loci for tubulin and phosphoglycerate kinase in Trypanozoon probably lie on the same chromosome, together with some variant surface glycoprotein genes; the genes for triose phosphate isomerase and glyceraldehyde phosphate dehydrogenase are separately located both with respect to each other and the above housekeeping genes. Therefore, there are at minimum three pairs of chromosomes carrying housekeeping genes in Trypanozoon. In some stocks the chromosomes carrying the tubulin and phosphoglycerate kinase genes are split into two bands, suggesting that homologous chromosomes may differ substantially in size in trypanosomes. One Trypanosoma (Nannomonas) congolense stock examined had a similar pattern of chromosome distribution to that of Trypanozoon, but with very small mini-chromosomes (25-50 kilobase pairs.)
Mol Biochem Parasitol 1986 Feb
PMID:Size-fractionation of the small chromosomes of Trypanozoon and Nannomonas trypanosomes by pulsed field gradient gel electrophoresis. 396 51


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>