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)

o-phthalaldehyde inactivates homodimeric, NADP+ dependent, 6-phosphogluconate dehydrogenase from sheep liver, upon formation of a single isoindole derivative per enzyme subunit. This indicates that the thiol group of a cysteine residue or the epsilon-amino group of a lysine residue located within 3 A and crosslinked by the reagent is essential for catalysis. Fluorescence analyses of the modified enzyme suggest that the isoindole derivative forms at the binding site of the nicotinamide moiety of NADP+. The enzymes from Trypanosoma brucei and Lactococcus lactis are also inactivated suggesting a similar three-dimensional structure in this domain. The isoindole derivative does not form with two mutants of the T. brucei enzyme (Lys185His and Lys185Leu), this allowing to identify not only the lysine but also the cysteine involved in the cross-linking. The formation of the isoindole derivative inactivates not only the oxidative decarboxylation, but also two partial reactions catalysed by the enzyme.
Biochem Mol Biol Int 1997 Sep
PMID:The cross-linking by o-phthalaldehyde of two amino acid residues at the active site of 6-phosphogluconate dehydrogenase. 931 93

The three-dimensional structure of 6-phosphogluconate dehydrogenase (6PGDH) from the parasitic protozoan Trypanosoma brucei has been solved at 2.8 A resolution. This pentose phosphate pathway enzyme is NADP-dependent; NADPH generated in the reaction protects against oxidative stress. The enzyme crystallises in the space-group P3121 with a dimer in the asymmetric unit and cell dimensions a=b=135.13 A, c=116.74 A, alpha=beta=90 degrees, gamma=120 degrees. The structure has refined to R=18.6% (Rfree=27.3%) with good geometry. The amino acid sequence of T. brucei 6PGDH is only 35% identical to that of the sheep liver enzyme and significant activity differences have been observed. The active dimer assembles with the C-terminal tail of one subunit threaded through the other, forming part of the substrate binding site. The tail of T. brucei 6PGDH is shorter than that of the sheep enzyme and its terminal residues associate tightly with the second monomer. The three-dimensional structure shows this generates additional interactions between the subunits close to the active site; the coenzyme binding domain is thereby associated more tightly with the helical domain. Three residues, conserved in all other known sequences, are important in creating a salt bridge between monomers close to the substrate binding site. The differences could explain the 200-fold enhanced affinity observed for the substrate analogue 6-phospho-2-deoxy-D-gluconate and suggest targets for anti-parasite drug design. The coenzyme binding domain of 6PGDH has a beta-alpha-beta fold; while in most species the "fingerprint" sequence is GxAxxG, in the T. brucei enzyme it is GxGxxG. Additional interactions between the enzyme and the coenzyme bis-phosphate are likely in the parasite 6PGDH, accounting for greater inhibition (40-fold) of 2'5'-ADP. While the core of the T. brucei dimer was restrained during refinement, several conformational differences have been found between the monomers; those at the coenzyme binding site suggest the molecule could be asymmetric during the enzyme reaction.
J Mol Biol 1998 Sep 25
PMID:A 2.8 A resolution structure of 6-phosphogluconate dehydrogenase from the protozoan parasite Trypanosoma brucei: comparison with the sheep enzyme accounts for differences in activity with coenzyme and substrate analogues. 973 29

An alternative method has been developed for isolating and culturing hepatocytes from livers of channel catfish. Hepatocytes are prepared using a collagenase-free perfusion system that relies on the chelating properties of ethylenediamine tetraacetic acid (EDTA). Hepatocyte yields of up to 3.6 x 10(8) cells per 100 g body weight have been achieved with initial viabilities routinely exceeding 95%. Cells isolated by this method and incubated in osmotically corrected culture medium at physiological pH have been maintained for several weeks in culture with minimal cell loss. During the first 24-48 h of culture, hepatocytes begin to link together and show structures that closely resemble those seen in intact liver (e.g. bile canaliculi, sinusoids). Cells cultured at 15 degrees C for 7 days maintain levels of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and lactate dehydrogenase (LDH), activity similar to those measured in vivo.
Comp Biochem Physiol A Mol Integr Physiol 1999 May
PMID:Non-enzymatic isolation and culture of channel catfish hepatocytes. 1042 27

The exact chemical composition of the red blood cell (RBC) membrane may vary depending on the methods used to isolate the membrane. We provide evidence here that RBC membrane can be fractionated by differential centrifugation and/or density gradient centrifugation into two distinct types, designated as 'heavy membrane' (HM) and 'light membrane' (LM). The amount of LM is twice that of HM on a per cell basis. HM and LM differ in some biochemical and electrophoretic properties. The total activities of Na+, K+- and Ca2+-ATPases, superoxide dismutase, glutathione peroxidase, catalase and glucose-6-phosphate and 6-phosphogluconate dehydrogenase are significantly higher in LM than HM on a per cell basis. While there is no significant difference in the specific activity of other enzymes between the two membranes, the specific activity of Ca2+-ATPase is significantly higher in HM, whereas Na+,K+-ATPase activity is higher in LM. There is a remarkable difference in the distribution of major ghost polypeptides between these two membranes. Component I of spectrin, component III and a protein with mol. wt. of 165 KDa are present in smaller amounts, whereas component II of spectrin and proteins with mol. wt. of 145, 84 and 76 KDa, respectively, are present in higher amounts in HM than LM. Some proteins such as band 4.1, 48 and 46 KDa are present only in LM, whereas some proteins with mol. wt. of 96, 78 and 43 KDa, respectively are present only in HM. It has been confirmed that these two membranes are not representatives of either (a) right side-out vs. inside out vesicles, or (b) open vs. sealed membranes. Thus HM and LM are two distinct membrane fractions. It is suggested that some part of the membrane is denser than other parts, and during hemolysis of RBCs, the rbc membrane is spliced resulting in two populations, dense and light.
Mol Cell Biochem 1999 Jun
PMID:Heterogeneity of human red blood cell membrane: co-existence of heavy and light membranes. 1044 13

Attachment of Salmonella typhimurium to epithelial surfaces elicit significant alterations in different cell signalling events which lead to the development of disease. The present investigation was conducted to evaluate the effect of immunization of rats with porins, on gut physiologic markers following challenge with S. typhimurium. Male albino Wistar rats were immunized with purified porins and challenged by intragastric infection with S. typhimurium. Electrolyte transport, levels of different second messengers and inflammatory mediators were studied. A net absorption of transepithelial fluxes of Na+ and Cl- in immunized-challenged group and secretion in infected group was found. Ca2+ and 3-O-methyl-D-glucose fluxes did not show any change. Significant increase in the levels of [Ca2+]i, cAMP, membrane form of protein kinase C, prostaglandins, NADPH oxidase, Glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, total oxygen free radicals, reactive nitrogen intermediates, citrulline and lipid peroxidation was found in the infected group. However, in the immunized-challenged group, the values of all the parameters were found to be almost the same as that of control as well as immunized groups. Na+, K+-ATPase and calmodulin levels were unaltered in all the groups of animals. The results of this study thus suggest that immunization of rats with purified Salmonella porins followed by subsequent challenge with the organism might be helpful for the prevention of multiple physiologic derangements in isolated ileal cells.
Mol Cell Biochem 1999 Nov
PMID:The effect of immunization with porins on gut pathophysiological response in rats infected with Salmonella typhimurium. 1063 Jun 36

The stability of liver and muscle enzymes and proteins in niacin-deficient quail towards trypsin treatment in the presence and absence of coenzymes, NAD or NADP, was characterized. The protection of liver dehydrogenases by coenzymes was low when they are subjected to trypsin digestion for 60 min. In contrast, in the muscle there was substantial protection against trypsin inactivation of glyceraldehyde-3-phosphate dehydrogenase by NAD and of 6-phosphogluconate dehydrogenase by NADP. Among all enzymes tested, glyceraldehyde-3-phosphate dehydrogenase showed the greatest protection against trypsin inactivation by NAD. SDS-polyacrylamide gel electrophoresis demonstrated that muscle proteins from the niacin-deficient group were more substantially protected compared to control and pair-fed groups when liver and muscle extracts were spiked with NAD and subjected to trypsin digestion. Overall results suggest that niacin deficiency exerted specific destabilizing effects on the stability of enzymes and proteins in muscle.
Comp Biochem Physiol B Biochem Mol Biol 2001 Jan
PMID:Effects of nicotinamide coenzymes on the stability of enzyme activities and proteins in niacin-deficient quail tissues against trypsin treatment. 1116 9

Previously we have shown that treatment with the peroxisome proliferator perfluorodecanoic acid (PFDA) significantly increased hepatic reduced glutathione (GSH) content without altering the activity of selenium-glutathione peroxidase. In this study we examined some potential mechanisms by which PFDA treatment increases GSH levels. Male Sprague-Dawley rats were given a single injection of 0, 8.8, 17.5, and 35 mg PFDA in corn oil per kg body weight. Twelve days later the effects of PFDA on the activities of enzymes associated with GSH synthesis, utilization, and regeneration were assessed. The results showed that in a dose-dependent manner, PFDA treatment significantly decreased the activity of gamma-glutamylcysteine synthetase, while the activities of NADPH-generating enzymes, malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase were increased. PFDA treatment also dose dependently decreased cytosolic, but not microsomal, glutathione S-transferase activity, and the activity of glutathione reductase was decreased by the highest dose of PFDA. The data obtained suggest that increased hepatic GSH levels following PFDA treatment may result from increased regeneration and/or decreased utilization.
J Biochem Mol Toxicol 2001
PMID:Peroxisome proliferator perfluorodecanoic acid alters glutathione and related enzymes. 1128 52

A number of triphenylmethane derivatives have been screened against 6-phosphogluconate dehydrogenase from Trypanosoma brucei and sheep liver. Some of these compounds show good inhibition of the enzymes and also selectivity towards the parasite enzyme. Modelling was undertaken to dock the compounds into the active sites of both enzymes. Using a combination of DOCK 3.5 and FLEXIDOCK a correlation was obtained between docking score and both activity for the enzymes and selectivity. Visualisation of the docked structures of the inhibitors in the active sites of the enzymes yielded a possible explanation of the selectivity for the parasite enzyme.
J Comput Aided Mol Des 2001 May
PMID:Selective inhibition of 6-phosphogluconate dehydrogenase from Trypanosoma brucei. 1139 39

Although polyploidization is rare among bivalve mollusks, recent cytogenetic studies have revealed a remarkable degree of genome amplification (up to 13n) in the freshwater bivalve family Sphaeriidae. We generated single-copy nuclear gene trees in order to test hypotheses addressing the evolutionary origins of sphaeriid genome duplication. Polyploid North American members of three cosmopolitan sphaeriid genera (Sphaerium, Musculium, and Pisidium) were characterized for their expressed allelic repertoire of a 526 nt c-DNA fragment of 6-phosphogluconate dehydrogenase (PGD). Pronounced levels of intra-individual genetic variation were uncovered in most of the polyploid taxa and a minority of alleles showed strong evidence of recombination. Phylogenetic analyses resolved polyploid sphaeriid PGD alleles into two clades (A, B), each of which contained a subsample of intra-individual allelic diversity of the genus Sphaerium. These two clades were also recovered in Musculium, however one (B) is represented here by a single recombinant allele. With the exception of a divergent segment in one putatively recombinant allele, the expressed PGD repertoire of the three Pisidium species investigated was restricted to one of the two clades (A). Major within-clade PGD gene tree branching patterns were congruent with mitochondrial gene tree topologies for these taxa. These results are inconsistent with a pattern of recent independent attainment of a polyploid status by our Sphaerium/Musculium study taxa and indicate that they may share a common genome duplication event predating the Miocene appearance of these two genera in the fossil record.
Mol Phylogenet Evol 2002 Oct
PMID:6-Phosphogluconate dehydrogenase (PGD) allele phylogeny is incongruent with a recent origin of polyploidization in some North American Sphaeriidae (Mollusca, Bivalvia). 1238 55

The pentose phosphate pathway (PPP) is the important metabolism pathway in plant. In the present study, a cDNA encoding one of the key enzymes of PPP, 6-phosphogluconate dehydrogenase(6PGDH), was isolated from rice and designated as Os6PGDH. The Os6PGDH encoding protein is a cytosolic isoenzyme according to the absence of plastid transit peptide at the N-terminus. The full-length cDNA of 1751 bp encodes 480 amino acids and its putative protein sequence is 94%, 84% and 83% identical to maize, spinach and alfalfa 6PGDHs respectively. Comparison of the cloned mRNA sequence with that of the genomic sequence from the Rice Genome Project showed a simple genomic organization devoid of introns in the translated region of the gene. RT-PCR experiments revealed that Os6PGDH expression was high in inflorescence, low in root and embryos but almost absent in leaves. Furthermore, Os6PGDH was up-regulated in the shoots under salt stress. It is suggested that 6PGDH in plant may play an important role in cell division and salt response.
Mol Biol Rep 2003 Dec
PMID:Molecular cloning and characterization of rice 6-phosphogluconate dehydrogenase gene that is up-regulated by salt stress. 1467 8


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