Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The preparation of 2-deoxy-2-amino-N-(5-dimethylamino-1-naphthalene sulfonyl)-glucose (III) designed as a fluorescent competitive inhibitor of hexokinase was achieved after reacting 2-deoxy-2-aminoglucose and 1-dimethylamino-5-naphthalene sulfonyl chloride. (III) showed fluorescence excitation and emission maxima in water at 330 and 507 nm, respectively. (III) was found to competitively inhibit hexokinase and a value of Ki = 3.0 x 10(-3)M was obtained for the system hexokinase B + Mg.ATP + glucose at pH 8.4.
 ...
PMID:Preparation and study of a fluorescent sugar analog competitive inhibitor of yeast hexokinase. 37 17

Fluorescence studies have been performed on yeast hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) as a function of temperature. Observations of both the intrinsic protein fluorescence and the fluorescence of the noncovalently bound apolar probe 2-(p-toluidinyl)naphthalene-6-sulfonic acid under conditions where hexokinase is monomeric, indicate that significant thermal structural transitions occur in the protein over the physiological range of temperature (0 degrees-40 degrees C) and that there are different temperature-dependent forms of the enzyme. Thermal transitions between these forms are affected by the binding of the substrates D-glucose and ATP-Mg. It therefore appears that catalysis connects conformers that differ in stability and the present results are consistent with models in which hexokinase function is linked to changes in the interactions between the domains into which this protein is folded.
 ...
PMID:A fluorescence study of thermally induced conformational changes in yeast hexokinase. 389 79

The fluorescent dye 6-(p-toluidinyl)naphthalene-2-sulfonic acid (2,6-TNS) has been shown to be a sensitive and nonperturbing probe of conformational states of yeast hexokinase. The binding of sugar ligands to hexokinase induced conformational states of the enzyme which could be distinguished by monitoring 2,6-TNS fluorescence and correlated well with their behavior during the catalytic reaction. The binding of five-carbon sugar inhibitors such as lyxose induced a conformational state of hexokinase that demonstrated a small quenching of 2,6-TNS fluorescence but an increased ability to bind metal-ligands when compared to free enzyme. The binding of good sugar substrates such as glucose produced a conformational state of hexokinase which demonstrated a large enhancement (37%) of bound 2,6-TNS fluorescence. This glucose-induced conformational state had an increased ability to bind metal-ATP ligands; however, the relative changes in the dissociation constants for the various metal-ATP ligands differ from those observed with hexokinase in the presence of lyxose. Hence, the lyxose-induced conformational state of hexokinase was concluded to be significantly different from the glucose-induced conformational state. The binding of poor sugar substrates such as 5-thioglucose induced a conformational state of hexokinase similar to the conformational state induced by glucose, but with a smaller enhancement of 2,6-TNS fluorescence (15%) and a lesser ability to increase the affinity for metal-ATP ligands. The six-carbon inhibitor with a bulky group on the 2-position, N-acetylglucosamine, gave minimal changes in 2,6-TNS fluorescence and effects on metal-nucleotide binding. These conformational states are interpreted in terms of the closure of the cleft between the two domains observed by X-ray crystallography. The binding of A1ATP to free hexokinase was not observed at concentrations up to 100 microM, which is consistent with the kinetic properties reported for this metal-ATP ligand. Although both CrATP and A1ATP have been reported to produce a slow burst-type transient in the progress curve of hexokinase, only CrATP demonstrated slow changes in 2,6-TNS fluorescence, indicating that the conformational state of hexokinase induced by A1ATP is different from the conformational state induced by CrATP.
 ...
PMID:6-(p-toluidinyl)naphthalene-2-sulfonic acid as a fluorescent probe of yeast hexokinase: conformational states induced by sugar and nucleotide ligands. 634 55

The degree of hydrophobic exposure in the molecular chaperone GroEL during its cycle of ATP hydrolysis was analyzed using 1,1'-bis(4-anilino)naphthalene-5,5'disulfonic acid (bisANS), a hydrophobic probe, whose fluorescence is highly sensitive to the environment. In the presence of 10 mM MgCl2 and 10 mM KCl the addition of ATP, but not ADP or AMP-PNP, resulted in a time-dependent, linear increase in the bisANS fluorescence. The rate of the increase in the bisANS fluorescence depended on the concentrations of both GroEL and the probe. The effect could be substantially inhibited by addition of excess ADP or by converting ATP to ADP using hexokinase, showing that the increase in the bisANS fluorescence was correlated with ATP hydrolysis. The rate of ATP hydrolysis catalyzed by GroEL was uncompetitively inhibited in the presence of bisANS. This uncompetitive inhibition suggests that the probe can interact with the GroEL-ATP complex. The inability of the nonhydrolyzable ATP analog, AMP-PNP, to cause a similar effect is explained by the interaction of bisANS with a transient conformational state of GroEL formed consequent to ATP hydrolysis. It is suggested that this short lived hydrophobic exposure reflects a conformational shift in GroEL that results from electrostatic repulsion between the bound products of ATP hydrolysis, and it plays an important role in the mechanism of the chaperonin cycle.
 ...
PMID:ATP hydrolysis is critical for induction of conformational changes in GroEL that expose hydrophobic surfaces. 905 67

The purpose of the study was to assess in female fish the possible interaction between treatment with a polycyclic aromatic hydrocarbon (PAH) like naphthalene and the onset of vitellogenesis. In a first experiment, female rainbow trout (Oncorhynchus mykiss) at stages 2-3 (previtellogenesis) or 4 (early vitellogenesis) were intraperitoneally injected (2 microl g(-1)) with vegetable oil alone (control) or containing naphthalene (50 mg kg(-1)) to be sampled 3 h later. A second experiment was similarly designed but using fish intraperitoneally implanted (10 microl g(-1)) with slow-release coconut oil implants alone (control) or containing 50 mg naphthalene kg(-1) body mass that were sampled 3 days after injection. On each sampling time, plasma levels of cortisol and 17beta-estradiol, and several metabolic parameters in plasma, liver and gonad were assessed. In controls, early vitellogenic fish compared with previtellogenic fish displayed changes that in some cases are confirmatory of previous studies whereas in other cases provide new information in plasma (increased amino acid levels), liver (decreased capacity for exporting glucose and reduced amino acid levels) and gonad (decreased amino acid levels). Naphthalene treatment produced in previtellogenic fish decreased 17beta-estradiol levels in plasma, increased plasma glucose or decreased liver gluconeogenic capacity whereas no major effects were noticed on parameters involved in lipid, amino acid and lactate metabolism. Differential effects of naphthalene treatment were noticed in early vitellogenic fish such as decreased 17beta-estradiol and glucose levels in plasma, increased hexokinase and glucokinase and lack of changes in fructose 1,6-bisphosphatase activities in liver, and a lower decrease of amino acid levels in gonad. Those alterations produced by naphthalene treatment resulted in a decreased capacity for covering the energy demand of vitellogenesis in liver and gonad that could contribute to a delay and/or impairment of the onset of maturation.
 ...
PMID:Interactive effects of naphthalene treatment and the onset of vitellogenesis on energy metabolism in liver and gonad, and plasma steroid hormones of rainbow trout Oncorhynchus mykiss. 1695 43