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

Two recombinant plasmids containing structural gene sequences of chick embryonic heart glyceraldehyde-3-phosphate dehydrogenase (GAP dehydrogenase) were constructed and characterized. The plasmids pGAP 30 and pGAP 36 have inserts of 1200 and 950 base pairs, respectively. The identity of the clones was established by hybrid-arrested and hybrid-selection translation assays, and by immunoprecipitation of hybrid-selected translation product with GaP dehydrogenase antiserum. Hybridization of labeled pGAP 30 DNA to size-fractionated chick heart poly(A) RNA occurred at the region on the gel corresponding to the mobility of GAP dehydrogenase mRNA. Base sequence analysis of plasmid pGAP 30 and the comparison of the amino acid sequence derived from it with that of pig muscle GAP dehydrogenase revealed that the amino acid sequence of GAP dehydrogenase is strictly conserved between the chick and pig muscle tissues. Expression of GAP dehydrogenase mRNA in developing chick heart cells in cultures was monitored by in situ hybridization. The GAP dehydrogenase mRNA was present in 5-h-old dividing myoblasts, in contrast to mRNAs specific for contractile proteins, which appear late in myoblast development paralleling morphogenetic differentiation of myoblasts into myocytes (Jakowlew, S. B., Khandekar, P., Datta, K., Narula, S. K., Arnold, H. H., and Siddiqui, M. A. Q. (1982) J. Mol. Biol. 156, 673-682).
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PMID:Cloning, partial sequencing, and expression of glyceraldehyde-3-phosphate dehydrogenase gene in chick embryonic heart muscle cells. 617 37

Protein-derived basic CD spectra for alpha-helix, antiparallel and parallel beta-structures, beta-bends and irregular form of proteins have been determined from the experimental CD spectra of six (myoglobin, lysozyme, ribonuclease A, papain, lactate dehydrogenase, subtilisin BPN') or seven (glyceraldehyde-3-phosphate dehydrogenase added) reference proteins and the analysis of the X-ray data. The secondary structures of thirteen proteins (seven reference and six additional ones) have been analysed using the basic CD spectra thus obtained. The data obtained have been compared with the results of the X-ray data analysis. It is shown that the accuracy of determination of the beta-structure and beta-bends contents using our basic CD spectra is about 2-3 times better than using the basic spectra reported by Chang et al. (Analyt. Biochem. 91, 13-31, 1978).
Mol Biol (Mosk)
PMID:[Determination of protein secondary structure from circular dichroism spectra. III. Protein-derived base spectra of circular dichroism for antiparallel and parallel beta-structures]. 627 89

This study presents the first evidence that the 5' promoter region of the Saccharomyces cerevisiae glyceraldehyde-3-phosphate dehydrogenase gene (G-3-PD) promoter will permit expression of an adjacent foreign gene. The S. cerevisiae G-3-PD promoter was linked to the herpes simplex virus--thymidine kinase (HSV-TK) gene in a shuttle plasmid capable of autonomous replication in both yeast and Escherichia coli. Since the HSV-TK gene promoter is not functional in yeast, yeast cells containing these plasmids will express the HSV-TK gene and synthesize thymidine kinase only if the yeast promoter fragment is fused to the HSV-TK gene in the proper orientation. The 5' flanking sequences necessary for the expression of heterologous eukaryotic genes in S. cerevisiae are discussed.
Mol Gen Genet 1984
PMID:Control of Herpes simplex virus thymidine kinase gene expression in Saccharomyces cerevisiae by a yeast promoter sequence. 632 18

Rat muscle glyceraldehyde-3-phosphate dehydrogenase is one of several enzymes which have been found to undergo age-related modifications. While the amount of this enzyme in muscle tissue does not change with age, both its specific activity and affinity towards its co-enzyme are significantly reduced in the old tissue. Age-related structural changes were found to exist in the nicotinamide binding site of the enzyme and the reactions leading to the activity loss in 'old' glyceraldehyde-3-phosphate dehydrogenase were shown to involve a reversible modification of the essential cysteine-149 residue at the active site of the enzyme. The aging effects were simulated by a controlled oxidation of cys-149 in samples of 'young' glyceraldehyde-3-phosphate dehydrogenase and subsequent reduction of this residue by 2-mercaptoethanol. The enzyme modified in this way closely resembles native 'old' glyceraldehyde-3-phosphate dehydrogenase, indicating that the structural modifications in the latter enzyme are indeed introduced by a post-translational process. The mechanism for aging of glyceraldehyde-3-phosphate dehydrogenase which is proposed, based on these observations, thus assumes an oxidation of cys-149 as its first step followed by irreversible conformational changes in the enzyme molecule. The aging of glyceraldehyde-3-phosphate dehydrogenase may thus be triggered by the reduced ability of old muscle tissue to protect its constituents against oxidation.
Mol Cell Biochem 1984
PMID:Age-related effects in enzyme catalysis. 636 9

Glyceraldehyde 3-phosphate dehydrogenase is a tetramer of four chemically identical subunits which requires the cofactor nicotinamide adenine dinucleotide (NAD) for activity. The structure of the holo-enzyme from Bacillus stearothermophilus has recently been refined using X-ray data to 2.4 A resolution. This has facilitated the structure determination of both the apo-enzyme and the enzyme with one molecule of NAD bound to the tetramer. These structures have been refined at 4 A resolution using the constrained-restrained parameter structure factor least-squares refinement program CORELS. When combined with individual atomic temperature factors from the holo-enzyme, these refined models give crystallographic R factors of 30.2% and 30.4%, respectively, for data to 3 A resolution. The apo-enzyme has 222 molecular symmetry, and the subunit structure is related to that of the holo-enzyme by an approximate rigid-body rotation of the coenzyme binding domain by 4.3 degrees with respect to the catalytic domains, which form the core of the tetramer. The effect of this rotation is to shield the coenzyme and active site from solvent in the holo-enzyme. In addition to the rigid-body rotation, there is a rearrangement of several residues involved in NAD binding. The structure of the 1 NAD enzyme is asymmetric. The subunit which contains the bound NAD adopts a conformation very similar to that of a holo-enzyme subunit, while the other three unliganded subunits are very similar to the apo-enzyme conformation. This result provides unambiguous evidence for ligand-induced sequential conformational changes in B. stearothermophilus glyceraldehyde 3-phosphate dehydrogenase.
J Mol Biol 1984 Sep 25
PMID:Structural evidence for ligand-induced sequential conformational changes in glyceraldehyde 3-phosphate dehydrogenase. 649 62

The thermolabile glyceraldehyde-3-phosphate dehydrogenase from the facultative thermophile Bacillus coagulans has a crystallographically exact 2-fold rotation axis of symmetry in one of its orthorhombic crystal forms (Lee et al., 1982). Using various crystallographic techniques, we have now identified this axis to be the molecular R-axis, which is the symmetry axis that relates the two subunits that form each active site of the tetrameric enzyme. This is in contrast to the symmetry of the human skeletal muscle enzyme wherein the crystallographically exact axis was found to be the Q-axis (Buehner et al., 1974). This finding could have important implications for the possible mechanism for the allosteric behavior of this molecule.
J Mol Biol 1983 Oct 05
PMID:Molecular symmetry of glyceraldehyde-3-phosphate dehydrogenase from Bacillus coagulans. 663 58

When the active-site carboxymethylated D-glyceraldehyde-3-phosphate dehydrogenase is irradiated with ultraviolet light in the presence of NAD+, a fluorescent NAD derivative that is covalently linked to the enzyme is obtained. A preliminary crystallographic study of this fluorescent derivative, as well as of the native and the carboxymethylated enzymes from Palinurus versicolor, showed that they are isomorphous and belong to space group C2 as reported for the native enzyme from Palinurus vulgaris. The three forms of the enzyme, although they have identical unit cell parameters, differ considerably in their diffraction patterns, indicating marked differences in conformation in spite of the fact that they differ chemically only in a restricted region around the active site.
J Mol Biol 1983 Dec 05
PMID:Preliminary crystallographic studies of lobster D-glyceraldehyde-3-phosphate dehydrogenase and the modified enzyme carrying the fluorescent derivative. 665 93

Apo-glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus and the partially saturated holo-enzyme can be crystallized isomorphously with the entire tetramer occupying the crystal asymmetric unit. For crystals that contain one molecule of NAD+ per tetramer the coenzyme is bound uniquely in one of the four available sites. The presence of NAD+ gives rise to nonequivalence in the binding of a heavy-atom compound to the subunits of the tetramer while for the apo-enzyme this binding is clearly symmetric. These results suggest that NAD binding gives rise to sequential ligand-induced structural changes of the tetramer, which may be responsible for the observed negative cooperativity in coenzyme binding.
J Mol Biol 1983 Apr 05
PMID:Coenzyme binding in crystals of glyceraldehyde-3-phosphate dehydrogenase. 684 6

Half-of-the-sites reactivity in oligomeric enzymes has generally been accepted as evidence for structural asymmetry between subunits. However, we show that the symmetric two-state allosteric model [Monod, J., Wyman, J., & Changeux, J.-P. (1965) J. Mol. Biol. 12, 88-118] is quantitatively consistent with half-of-the-sites reactivity data for several hexameric and tetrameric enzymes. Specifically, the time courses for both the modification and the inactivation of glutamate dehydrogenase by glutamyl alpha-chloromethyl ketone and uridine diphosphoglucose dehydrogenase by 5-(iodoacetamidoethyl)aminonaphthalene-1-sulfonic acid are fit with just five parameters for each enzyme-modifier pair. In the case of glyceraldehyde-3-phosphate dehydrogenase, the time courses for modification of the yeast enzyme by iodoacetic acid and the rabbit-muscle enzyme by 3,3,3-trifluorobromoacetone are fit with the same model, and parameter values from these fits are used to generate theoretical inactivation curves which are found to agree well with the experimentally measured inactivation. We conclude that half-of-the-sites reactivity, if it is not an artifact of residual heterogeneity, could be a kinetic phenomenon related to metastability of partially modified states of a symmetric oligomer and that asymmetry between subunits should therefore not necessarily be inferred from such behavior. If similar metastability occurs in substrate binding, it may play a significant role in mechanism of catalysis and control. In such cases, the virtual inaccessibility of the substrate binding equilibrium would preclude conventional quasi-equilibrium models for the enzyme kinetics.
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PMID:Molecular symmetry and metastable states of enzymes exhibiting half-of-the-sites reactivity. 702 97

The extra-cellular matrix has been demonstrated to play an important role in the differentiation of a number of cell types in vitro. The purpose of this study was to establish the role of ECM collagen synthesis in regulating growth and differentiation of embryonic cardiocytes in vitro. We report that treatment of embryonic cardiocytes in vitro with two chemically distinct inhibitors of collagen synthesis, cis-hydroxy-L-proline and ethyl-3,4-dihydroxybenzoate, effectively inhibits collagen secretion. This results in disruption of myofibrillogenesis as seen by immunocytochemistry and electron microscopy, and absence of beating. The expression of muscle specific genes TroponinT and Myosin Heavy Chain are reduced, while the expression of the housekeeping gene glyceraldehyde phosphate dehydrogenase is uneffected. All of these effects are reversible. The structural effects are not prevented by growing the cells on various substrates, including denatured collagen, collagen type IV, laminin and Matrigel. Thus, inhibition of collagen secretion disrupts myofibrillogenesis and results in the alteration of expression of muscle-specific genes, suggesting that collagen synthesis plays an essential role in maintaining the differentiated phenotype of cardiocytes.
J Mol Cell Cardiol 1994 Jun
PMID:Collagen synthesis inhibitors disrupt embryonic cardiocyte myofibrillogenesis and alter the expression of cardiac specific genes in vitro. 752 75


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