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Clinica Chimica Acta; International... Dec 1980Phosphoglycerate kinase deficiency is a rate, X-linked disorder associated with a severe haemolytic anaemia. In general the deficiency has been demonstrated only in...
Phosphoglycerate kinase deficiency is a rate, X-linked disorder associated with a severe haemolytic anaemia. In general the deficiency has been demonstrated only in erythrocytes and leucocytes. However, in a subject with this condition, the activity of phosphoglycerate kinase in lymphocytes and platelets was also shown to be less than 5% of the normal value. Following the death of this subject in 1979, the deficiency was also found to occur in tissue samples of brain, skeletal muscle, liver and cardiac muscle, obtained at the autopsy. Values for phosphoglycerate kinase were of the order of 0.5-5% of normal controls. Other glycolytic enzymes which were tested were hexokinase, pyruvate kinase, enolase and 2-phosphoglyceromutase. In general, values for these enzymes were either normal or slightly raised.
Topics: Adolescent; Adult; Anemia, Hemolytic, Congenital; Blood Cells; Female; Glycolysis; Hexokinase; Humans; Male; Middle Aged; Phosphoglycerate Kinase; Phosphoglycerate Mutase; Phosphopyruvate Hydratase; Pyruvate Kinase; Tissue Distribution
PubMed: 6256101
DOI: 10.1016/0009-8981(80)90018-2 -
Pediatric Hematology and Oncology Feb 2023The enzyme phosphoglycerate kinase 1 (PGK1) catalyzes the first ATP producing reaction in the glycolysis pathway. Certain mutations to the coding gene of present...
The enzyme phosphoglycerate kinase 1 (PGK1) catalyzes the first ATP producing reaction in the glycolysis pathway. Certain mutations to the coding gene of present clinically with varying manifestations including hemolytic anemia, central nervous system (CNS) dysfunction and myopathy. Various mutations have been described in the literature at the clinical and molecular level. Herein, we describe a novel case mutation ( Galveston) in a 4-year-old boy who presented with all three manifestations. We discuss the characteristic hematopathology findings from this patient as well as provide a comparison with previously described neuroimaging findings. The variable clinical presentation of this condition along with its inherent uniqueness provide a diagnostic challenge for physicians. This presentation will add to the current body of knowledge for this condition and help guide future investigation and management.
Topics: Male; Humans; Child; Child, Preschool; Phosphoglycerate Kinase; Metabolism, Inborn Errors; Anemia, Hemolytic; Muscular Diseases
PubMed: 35608390
DOI: 10.1080/08880018.2022.2072987 -
Neurology Mar 2000The authors report a 36-year-old man with exertional myoglobinuria and muscle cramp without hemolytic anemia or CNS symptoms. They found a deficiency of phosphoglycerate...
The authors report a 36-year-old man with exertional myoglobinuria and muscle cramp without hemolytic anemia or CNS symptoms. They found a deficiency of phosphoglycerate kinase (PGK) activity in muscle and erythrocytes and a 4-base pair deletion in exon 6 of the PGK gene. This mutation may cause a frameshift, yielding an abnormal stop codon in exon 6 by which a truncated PGK protein was produced. This phenotype is caused by a novel mutation of the PGK gene.
Topics: Adult; Anemia, Hemolytic; Central Nervous System Diseases; Humans; Male; Muscular Diseases; Phosphoglycerate Kinase; Polymerase Chain Reaction
PubMed: 10720297
DOI: 10.1212/wnl.54.5.1188 -
Acta Crystallographica. Section D,... Dec 2002The crystallographic structure of a circularly permuted form of yeast PGK, 72p yPGK, has been determined to a resolution of 2.3 A by molecular replacement. In this...
The crystallographic structure of a circularly permuted form of yeast PGK, 72p yPGK, has been determined to a resolution of 2.3 A by molecular replacement. In this engineered protein, the C- and N-terminal residues of the wild-type protein are directly connected by a peptide bond and new N- and C-terminal residues are located within the N-terminal domain. The overall fold of the protein is very similar to that of the wild-type protein, directly demonstrating that the continuity of a folding unit is not relevant to the folding process of the whole protein. Only limited structural changes were observed: these were in the regions associated with the new connection, in a long flexible loop in the permuted domain and in the vicinity of Arg38, a functionally important residue. The relative positions of the two domains suggested that this permuted protein adopts one of the most open/twisted conformations seen amongst PGKs of known structure. The effect of the mutation on the functional properties is more easily accounted for by a restriction of hinge-bending motion than by structural changes in the protein.
Topics: Crystallography, X-Ray; Models, Molecular; Phosphoglycerate Kinase; Protein Conformation; Saccharomyces cerevisiae
PubMed: 12454459
DOI: 10.1107/s0907444902015548 -
Proteins May 2000Yeast phosphoglycerate kinase is a structurally well-characterized enzyme consisting of 415 amino acids without disulfide bonds. Anion-induced refolding from its...
Yeast phosphoglycerate kinase is a structurally well-characterized enzyme consisting of 415 amino acids without disulfide bonds. Anion-induced refolding from its acid-unfolded state gives rise to the formation of worm-like amyloid fibrils with a persistence length of 73 nm. Electron microscopy and small-angle X-ray scattering data indicate that the fibrils have an elliptical cross-section with dimensions of 10.2 nm x 5.1 nm. About half of all amino acids are organized in form of cross-beta structure which gives rise to typical infrared spectra, X-ray diffraction and yellow-green birefringence after Congo red staining. The kinetics of amyloid formation, monitored by infrared spectroscopy, dynamic light scattering and X-ray scattering, was found to be strongly dependent on protein concentration. The infrared data indicate that the formation of cross-beta structure practically comes to an end already after some hours, whereas the length-growth of the amyloid fibrils, monitored by small-angle X-ray scattering, was not yet completed after 1,300 hours.
Topics: Amyloid; Congo Red; Light; Microscopy, Electron; Phosphoglycerate Kinase; Protein Folding; Protein Structure, Quaternary; Saccharomyces cerevisiae; Scattering, Radiation; Spectrophotometry, Infrared; X-Rays
PubMed: 10737941
DOI: 10.1002/(sici)1097-0134(20000515)39:3<204::aid-prot20>3.0.co;2-8 -
Experimental Parasitology Apr 2018T. rangeli epimastigotes contain only a single detectable phosphoglycerate kinase (PGK) enzyme in their cytosol. Analysis of this parasite's recently sequenced genome...
T. rangeli epimastigotes contain only a single detectable phosphoglycerate kinase (PGK) enzyme in their cytosol. Analysis of this parasite's recently sequenced genome showed a gene predicted to code for a PGK with the same molecular mass as the natural enzyme, and with a cytosolic localization as well. In this work, we have partially purified the natural PGK from T. rangeli epimastigotes. Furthermore, we cloned the predicted PGK gene and expressed it as a recombinant active enzyme. Both purified enzymes were kinetically characterized and displayed similar substrate affinities, with Km values of 0.13 mM and 0.5 mM, and Km values of 0.28 mM and 0.71 mM, for the natural and recombinant enzyme, respectively. The optimal pH for activity of both enzymes was in the range of 8-10. Like other PGKs, TrPGK is monomeric with a molecular mass of approximately 44 kDa. The enzyme's kinetic characteristics are comparable with those of cytosolic PGK isoforms from related trypanosomatid species, indicating that, most likely, this enzyme is equivalent with the PGKB that is responsible for generating ATP in the cytosol of other trypanosomatids. This is the first report of a glycolytic enzyme characterization from T. rangeli.
Topics: Amino Acid Sequence; Base Sequence; Chromatography, Gel; Chromatography, Ion Exchange; Cloning, Molecular; Consensus Sequence; Cytosol; DNA, Intergenic; Hydrogen-Ion Concentration; Isoenzymes; Kinetics; Phosphoglycerate Kinase; Recombinant Proteins; Sequence Alignment; Trypanosoma rangeli
PubMed: 29526574
DOI: 10.1016/j.exppara.2018.03.009 -
Nature Jan 1974
Topics: Adenosine Diphosphate; Binding Sites; Phosphoglycerate Kinase; Protein Conformation; Saccharomyces cerevisiae; X-Ray Diffraction
PubMed: 4587639
DOI: 10.1038/247014a0 -
Biochimica Et Biophysica Acta Apr 1978Yeast 3-phosphoglycerate kinase (ATP:3-phospho-D-glycerate 1-phospho-transferase, EC 2.7.2.3) is inactivated by phenylglyoxal. Loss of activity correlates with the...
Yeast 3-phosphoglycerate kinase (ATP:3-phospho-D-glycerate 1-phospho-transferase, EC 2.7.2.3) is inactivated by phenylglyoxal. Loss of activity correlates with the modification of two arginyl residues, both of which are protected by all of the substrates. The modification is not accompanied by any significant conformational change as determined by optical rotatory dispersion. Ultraviolet difference spectrophotometry indicates that the inactivated enzyme retains its capacity for binding the nucleotide substrates whereas the spectral perturbation characteristic of 3-phosphoglycerate binding is abolished in the modified enzyme. The data suggest that at least one of the two essential arginyl residues is located at or near the 3-phosphoglycerate binding site. A likely role of this residue could be its interaction with the negatively charged phosphate or carboxylate groups of 3-phosphoglycerate.
Topics: Arginine; Binding Sites; Kinetics; Phosphoglycerate Kinase; Protein Binding; Saccharomyces cerevisiae; Spectrophotometry, Ultraviolet
PubMed: 350284
DOI: 10.1016/0005-2744(78)90039-6 -
Journal of Biochemistry Jun 1979(1) A glycolytic enzyme, phosphoglycerate kinase [EC 2.7.2.3], was purified from cells of an extreme thermophile, Thermus thermophilus strain HB8. The enzyme was... (Comparative Study)
Comparative Study
(1) A glycolytic enzyme, phosphoglycerate kinase [EC 2.7.2.3], was purified from cells of an extreme thermophile, Thermus thermophilus strain HB8. The enzyme was resistant to heat, and no loss of activity was observed after incubation for 10--20 min at 79 degrees C. (2) Catalytic properties such as pH optimum (pH 6--8.5), kinetic parameters (Km=0.28 mM for ATP, 1.79 mM for glycerate 3-phosphate), substrate specificity and inhibitors of the enzyme were investigated and compared with those of phosphoglycerate kinase from other sources. (3) The enzyme protein consists of a single polypeptide chain of molecular weight 44,600. The isoelectric point is 5.0 The amino acid composition of the enzyme was studied. The contents of ordered secondary structures were estimated to be 29% alpha-helix and 11% pleated sheet from the circular dichroic spectrum of the enzyme protein. (4) The fluorescence spectrum of the enzyme protein showed an emission maximum at 320 nm when excited at 280 nm. The quantum yield was 0.19. Tryptophyl fluorescence was not quenched, in contrast to the fluorescence reported for yeast phosphoglycerate kinase.
Topics: Amino Acids; Circular Dichroism; Geobacillus stearothermophilus; Kinetics; Molecular Weight; Phosphoglycerate Kinase; Protein Conformation; Species Specificity; Spectrometry, Fluorescence; Substrate Specificity; Thermus
PubMed: 457645
DOI: 10.1093/oxfordjournals.jbchem.a132480 -
Seizure Apr 2024
Topics: Humans; Phosphoglycerate Kinase; Male; Joint Instability; Female; Spinal Diseases; Metabolism, Inborn Errors; Genetic Diseases, X-Linked
PubMed: 38432079
DOI: 10.1016/j.seizure.2024.02.010