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)

Duocarmycin A is an antitumour antibiotic that binds covalently to the minor groove N-3 position of adenine with sequence specificity for the 3'-adenine in a d(A-A-A-A) tract in duplex DNA. The adenine ring becomes protonated on duocarmycin adduct formation resulting in charge delocalization over the purine ring system. We report on the solution structure of duocarmycin A bound site specifically to A12 (designated *A12+) in the sequence context d(T3-T4-T5-T6).d(A9-A10-A11-*A12+) within a hairpin duplex. The solution structure was solved based on a combined NMR-molecular dynamics study including NOE based intensity refinement. The A and B-rings of duocarmycin are positioned deep within the walls of the minor groove with the B-ring (which is furthest from the covalent linkage site) directed towards the 5'-end of the modified strand. Duocarmycin adopts an extended conformation and is aligned at approximately 45 degrees to the helix axis with its non-polar concave edges interacting with the floor of the minor groove while its polar edges are sandwiched within the walls of the minor groove. The T3.*A12+ modification site pair forms a weak central Watson-Crick hydrogen bond in contrast to all A.T and G.C pairs, which align through standard Watson-Crick pairing in the complex. The helical parameters are consistent with a minimally perturbed right-handed duplex in the complex with minor groove width and x-displacement parameters indicative of a B-form helix. A striking feature of the complex is the positioning of duocarmycin A within the walls of the minor groove resulting in upfield shifts of the minor groove sugar protons, as well as backbone proton and phosphorus resonances in the DNA segment spanning the binding site.
J Mol Biol 1995 Apr 21
PMID:Solution structure of the covalent duocarmycin A-DNA duplex complex. 773 Oct 41

High energy phosphates [phosphocreatine (PCr) and adenosine triphosphate (ATP)] are maintained in the heart under conditions of altered myocardial contractility and under certain conditions of maintained in the heart under conditions of altered myocardial contractility and under certain conditions of myocardial ischemia (such as hibernating myocardium). However, the metabolic consequences of reduced regional contractility have not been investigated. This study was designed to test the hypotheses that (1) under conditions of normal blood flow, reduction in regional contractility does not result in changes in PCr or ATP and (2) under conditions of reduced blood flow, reduction in regional contractility prevents the expected decline in high energy phosphates usually seen in regional ischemia. An in situ open chest swine preparation was used in which regional contractility was reduced with the administration of intracoronary lidocaine. High energy phosphates were measured using phosphorus-31 magnetic resonance spectroscopy (NMR) under conditions of normal flow and reduced flow. Intracoronary lidocaine infusion in 9 animals did not change blood flow from basal levels, but significantly reduced regional segment shortening from 0.16 +/- 0.02 to 0.02 +/- 0.01. The ratio of PCr/ATP did not change with lidocaine infusion (control: 1.53 +/- 0.09; lidocaine: 1.59 +/- 0.11), but oxygen content in the anterior interventricular vein increased from 8.25 +/- 0.69 to 9.83 +/- 0.91 ml/O2/100 ml blood in parallel studies (P = 0.04). While the lidocaine infusion was maintained, subsequent coronary stenosis significantly reduced subendocardial blood flow from 0.91 +/- 0.06 to 0.41 +/- 0.06 ml/min/g without significantly altering high energy phosphates (PCr/ATP = 1.51 +/- 0.15). In contrast to the 29% decline in PCr previously seen with regional ischemia, PCr was unchanged with this degree of flow reduction in the presence of lidocaine. Thus, PCr and ATP are unchanged under conditions of reduced contractility, consistent with equilibrium of energy synthesis and utilization. In addition, factors which reduce myocardial contractility, either pharmacologically or endogenously, protect against the metabolic consequences of reduced flow by reducing MVO2.
J Mol Cell Cardiol 1994 Dec
PMID:Effects of regional myocardial lidocaine infusion on high energy phosphates. 773 Oct 55

Phosphorus magnetic resonance spectroscopy (31P-MRS) has emerged as a noninvasive reliable tool for in vivo study of human tissue bioenergetics. It detects and quantifies some phosphorylated compounds present in millimolar concentration inside the cell, including ATP, phosphocreatine (PCr) and inorganic phosphate (Pi). By 31P-MRS we studied brain and skeletal muscle energy metabolism of three patients with retinitis pigmentosa before and after oral coenzyme Q10 (CoQ10) (100 mg/day). Before treatment we found a low PCr content in the brains of all patients, accompanied by a high [Pi] and high [ADP]. In two of three patients CoQ10 treatment resulted in a larger brain energy reserve mainly shown by an increased [PCr]. Abnormal muscle mitochondrial function was found only in one patient as shown by a reduced rate of PCr resynthesis after exercise. In this patient CoQ10 treatment resulted in an increased rate of PCr resynthesis. Our observations indicate that CoQ10 can improve mitochondrial functionality in the brain and skeletal muscle of patients with retinitis pigmentosa.
Mol Aspects Med 1994
PMID:The use of phosphorus magnetic resonance spectroscopy to study in vivo the effect of coenzyme Q10 treatment in retinitis pigmentosa. 775 34

Changes in the concentrations of phosphorus containing metabolites were monitored by 31P NMR in the uteri of hamsters during the estrous cycle. Concentrations of phosphocreatine (PCr) and ATP were significantly increased in estrus animals compared to diestrus animals. Concentrations of these metabolites were also increased in immature female hamsters and ovariectomized (OVX) adult hamsters treated with estradiol indicating that estradiol was responsible for this effect. However, the steroid hormones progesterone and testosterone did not increase the concentrations of the phosphorus containing metabolites. Further, immature female hamsters also following treatment with estradiol showed an initial decline in phosphomonoester (PME), PCr, ATP and inorganic phosphate but by 24 h of treatment the concentrations returned to control levels. The NMR study also revealed that the intracellular pH of the hamster uterus was around 7.4 all through the estrous cycle.
J Steroid Biochem Mol Biol 1995 Jun
PMID:31P NMR study of phosphorus containing metabolites in the uterus of hamster: changes during the estrous cycle and the effect of hormonal manipulation. 777 63

The rare earth gadolinium (Gd) is used in modern industry. Solubilized DTPA Gd and DOTA Gd complexes are used as contrast media in nuclear magnetic resonance imaging. In order to determine the subcellular localization of Gd, rats were injected intraperitoneally with Gd nitrate. Two microanalytic methods, ion microanalysis and electron microprobe, enabled the distribution and the intracellular localization of Gd to be determined in the liver, spleen, bone marrow, kidneys and lung. The results showed: a) a punctual distribution of Gd in the tissues (liver, spleen, bone marrow and lung) as observed by ion microscopy; b) a selective concentration of Gd in the lysosomes of macrophages of the liver (hepatocytes), spleen (macrophages), bone marrow (macrophages) and lung (phagocyte cells), as determined by electron probe X-ray microanalysis. In all these sites the Gd is associated to phosphorus. Results are compared to those found for other rare earths and metal elements.
Cell Mol Biol (Noisy-le-grand) 1995 Mar
PMID:Subcellular localization of gadolinium injected as soluble salt in rats: a microanalytical study. 778 37

Analysis of phospholipid and their fatty acid composition of human intestinal mucosa was performed by an method elaborated to analyze the limited amount of sample with 2-dimensional TLC followed by lipid-phosphorus determination. Using this method, plasmenylethanolamine was detected in human intestinal mucosa and accounted for about 7% of phospholipid in small and large intestinal mucosa. The amounts of polyunsaturated fatty acids of phosphatidylethanolamine were higher than those of other phosphoglycerides in intestinal mucosa, hence, inflammation-related eicosanoids may originate from ethanolamine containing phospholipid.
Biochem Mol Biol Int 1994 Jun
PMID:Plasmenylethanolamine in human intestinal mucosa detected by an improved method for analysis of phospholipid. 795 Oct 64

To elucidate the role of bicarbonate-dependent mechanisms and Na+/H+ exchange in maintenance of physiological intracellular pH (pHi) under various steady-state conditions, phosphorus NMR spectra were taken in isovolumically-contracting, perfused ferret hearts. Switching the perfusate from HCO3-/CO2 to HEPES buffer significantly decreased pHi from the control value of 7.14 +/- 0.01 (mean +/- S.E., n = 4) to 7.08 +/- 0.01 (P < 0.01). Exposure to 4-acetamide-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS; 10(-4) M) a blocker of anion exchange (7.12 +/- 0.01 in control, 7.07 +/- 0.02 with SITS, n = 6, P < 0.05), led to acidification of pHi. Ethylisopropylamiloride (EIPA; 10(-6) M), a blocker of the Na+/H+ exchange, induced a decrease in pHi (7.17 +/- 0.01 in control, 7.11 +/- 0.01 with EIPA, n = 5, P < 0.05). Lowering [Cl-] in the perfusate (7.14 +/- 0.02 in control, 7.09 +/- 0.03 with low-[Cl]o perfusate, n = 5, P < 0.01) also decreased pHi, perhaps by a non-bicarbonate-dependent mechanism. These results indicate that both bicarbonate-dependent mechanisms and Na+/H+ exchange contribute significantly and additively to the maintenance of physiological pHi in isovolumically contracting, perfused hearts.
J Mol Cell Cardiol 1994 Jul
PMID:Control of steady-state intracellular pH in intact perfused ferret hearts. 796 50

NUC-1, a positive regulatory protein of Neurospora crassa, controls the expression of several unlinked target genes involved in phosphorus acquisition. The carboxy-terminal end of the NUC-1 protein has sequence similarity to the helix-loop-helix family of transcription factors. Bacterially expressed and in vitro-synthesized proteins, which consist of the carboxy-terminal portion of NUC-1, bind specifically to upstream sequences of two of its target genes, pho2+ and pho-4+. These upstream sequences contain the core sequence, CACGTG, a target for many helix-loop-helix proteins. A large loop region (47 amino acids) separates the helix I and helix II domains. Mutations and deletion within the loop region did not interfere with the in vitro or in vivo functions of the protein. Immediately carboxy-proximal to the helix II domain, the NUC-1 protein contains an atypical zipper domain which is essential for function. This domain consists of a heptad repeat of alanine and methionine rather than leucine residues. Analysis of mutant NUC-1 proteins suggests that the helix II and the zipper domains are essential for the protein dimerization, whereas the basic and the helix I domains are involved in DNA binding. The helix I domain, even though likely to participate in dimer formation while NUC-1 is bound to DNA, is not essential for in vitro dimerization.
Mol Cell Biol 1994 Dec
PMID:Analysis of the DNA-binding and dimerization activities of Neurospora crassa transcription factor NUC-1. 796 22

The detailed chemical composition and microstructure of freshly deposited bone mineral, and how these properties change with maturation of the mineral, have been studied intensively and still remain controversial. For example, current analytical technology is inadequate for the unambiguous characterization of the monohydrogen phosphate ions in bone mineral. Using a differential cross polarization/magic angle spinning solid state nuclear magnetic resonance spectroscopy technique, we suppress the dominant orthophosphate (PO4-3) signal to reveal the spectra of the minor phosphate constituents. This method depends upon differences in the cross polarization time constants for phosphorus-31 nuclei in protonated and non-protonated phosphate ions. It is now possible for the first time to directly measure both the proportion of acid phosphate (HPO4-2) as well as the parameters which characterize its isotropic and anisotropic chemical shift. In bone from three species at several developmental stages, we have found a single type of acid phosphate species, identical in all of the specimens examined. The phosphorus-31 isotropic chemical shift of this acid phosphate group in bone mineral corresponds precisely with that of acid phosphate in octacalcium phosphate, and not with that of brushite. In contrast, the bone acid phosphate anisotropic chemical shift parameters are close to those of brushite, and differ significantly from those of octacalcium phosphate. The orthophosphate resonances of bone mineral, synthetic hydroxyapatite and synthetic octacalcium phosphate share identical chemical isotropic shifts, and similar chemical shift anisotropies. The implication of these results is that the intimate structure of the acid phosphate group in bone mineral is unique, and that none of the common synthetic calcium phosphates accounts well for all of the observed solid state phosphorus-31 NMR properties of bone mineral.
J Mol Biol 1994 Dec 09
PMID:A unique protonated phosphate group in bone mineral not present in synthetic calcium phosphates. Identification by phosphorus-31 solid state NMR spectroscopy. 799 Jan 31

We administered ethanol to pregnant rats and determined cholesterol, lipid phosphorus and fluorescence anisotropy of diphenylhexatriene (DPH) and of trimethylaminophenyl hexatriene (TMA-DPH) in erythrocyte ghosts of newborn pups and of their mothers. Cholesterol content was different in dams and pups and changed after treatment. Age, but not ethanol, affected lipid phosphorus. Either age (dams versus pups) or treatment affected the curves of DPH fluorescence anisotropy (r) versus temperature (T), but those of TMA-DPH did not change, indicating that only the inner core of the membrane was influenced. We conclude that adult and erythrocyte ghosts differed for the lipid composition, for the dependence of r on T (for DPH) and for the effects of ethanol dosing on these parameters.
Biochem Mol Biol Int 1994 May
PMID:The effect of maternal ethanol intoxication on erythrocyte ghost fluidity in new-born rat pups. 808 Nov 99


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