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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of kinetic measurements of peptide dissociation from class II MHC-peptide complexes provide compelling evidence for the existence of conformational isomers in solution. There is evidence that T-lymphocytes can distinguish such isomers. However, virtually nothing is known about the structure of these isomers. Accordingly, we have investigated a water-soluble version of the murine class II MHC molecule I-Ek complexed with an antigenic peptide derived from pigeon cytochrome c residues 89-104 (PCC) by 19F-NMR. Two fluorine labels were placed on the PCC peptide; one fluorine label was placed at a MHC contact site, the other at a position involved in T-cell receptor (TCR) recognition. Introduction of these labels did not alter the observed kinetics of the PCC/I-Ek complex. The NMR data show two conformational isomers of this immunogenic complex. The presence of conformational isomers at a TCR contact site suggests that these structures may be recognized differently by the TCR. The agreement between the dissociation kinetics and the 19F-NMR data demonstrate that kinetic heterogeneity is correlated with structural counterparts observed by NMR. Dissociations in the presence of dimethyl sulfoxide were used to show that the rate of interconversion of these conformational isomers at pH 7.0 is low, with a lifetime on the order of hours or more. Modification of a peptide residue of PCC occupying the minor MHC binding pocket P6 alters the 19F-NMR spectra of both labels. This demonstrates that distant changes of amino acid residues can influence the conformation of the whole antigenic peptide inside the MHC binding cleft.
J Mol Biol 1999 Feb 12
PMID:Conformational isomers of a class II MHC-peptide complex in solution. 993 Dec 60

How is the native structure encoded in the amino acid sequence? For the traditional backbone centric view, the dominant forces are hydrogen bonds (backbone) and phi-psi propensity. The role of hydrophobicity is non-specific. For the side-chain centric view, the dominant force of protein folding is hydrophobicity. In order to understand the balance between backbone and side-chain forces, we have studied the contributions of three components of a beta-hairpin peptide: turn, backbone hydrogen bonding and side-chain interactions, of a 16-residue fragment of protein G. The peptide folds rapidly and cooperatively to a conformation with a defined secondary structure and a packed hydrophobic cluster of aromatic side-chains. Our strategy is to observe the structural stability of the beta-hairpin under systematic perturbations of the turn region, backbone hydrogen bonds and the hydrophobic core formed by the side-chains, respectively. In our molecular dynamics simulations, the peptides are solvated. with explicit water molecules, and an all-atom force field (CFF91) is used. Starting from the original peptide (G41EWTYDDATKTFTVTE56), we carried out the following MD simulations. (1) unfolding at 350 K; (2) forcing the distance between the C(alpha) atoms of ASP47 and LYS50 to be 8 A; (3) deleting two turn residues (Ala48 and Thr49) to form a beta-sheet complex of two short peptides, GEWTYDD and KTFTVTE; (4) four hydrophobic residues (W43, Y45, F52 and T53) are replaced by a glycine residue step-by-step; and (5) most importantly, four amide hydrogen atoms (T44, D46, T53, and T55, which are crucial for backbone hydrogen bonding), are substituted by fluorine atoms. The fluorination not only makes it impossible to form attractive hydrogen bonding between the two beta-hairpin strands, but also introduces a repulsive force between the two strands due to the negative charges on the fluorine and oxygen atoms. Throughout all simulations, we observe that backbone hydrogen bonds are very sensitive to the perturbations and are easily broken. In contrast, the hydrophobic core survives most perturbations. In the decisive test of fluorination, the fluorinated peptide remains folded under our simulation conditions (5 ns, 278 K). Hydrophobic interactions keep the peptide folded, even with a repulsive force between the beta-strands. Thus, our results strongly support a side-chain centric view for protein folding.
J Mol Biol 2000 Mar 03
PMID:Molecular dynamics simulations of a beta-hairpin fragment of protein G: balance between side-chain and backbone forces. 1068 6

The rotational spectrum of AsH(2) in its ground &Xtilde;(2)B(1) electronic state has been recorded using a far-infrared laser magnetic resonance spectrometer. The AsH(2) radical was produced inside the spectrometer cavity by the reaction of arsine (AsH(3)) with fluorine atoms. Hyperfine splittings from both (75)As and (1)H nuclei were observed, and analysis of the spectra has yielded accurate values for rotational, hyperfine, and Zeeman parameters. Copyright 2000 Academic Press.
J Mol Spectrosc 2000 Apr
PMID:Rotational Spectrum of the AsH(2) Radical in Its Ground State, Studied by Far-Infrared Laser Magnetic Resonance. 1070 34

This study was undertaken to clarify the role of high-energy phosphate metabolism in hydrogen peroxide-induced cardiac dysfunction using phosphorus and fluorine nuclear magnetic resonance spectroscopy. The exposure of a Langendorff-perfused heart to hydrogen peroxide (200-400 micromol/L, 8 min) provoked biphasic contractile dysfunction characterized by a transient depression of left ventricular developed pressure during the administration of hydrogen peroxide and a delayed elevation of left ventricular end-diastolic pressure after the washout of hydrogen peroxide. The initial phase of cardiac dysfunction correlated well with the accumulation of sugar phosphates (r = 0.89, p < 0.01). Furthermore, we demonstrated that glibenclamide, a potent inhibitor of the ATP-sensitive K+ channel, attenuated the initial depression of developed pressure. On the other hand, the delayed elevation of end-diastolic pressure correlated well with the total ATP depletion (r = 0.96, p < 0.01). However, ATP loss was supposed to be a mere result from the increased ATP consumption corresponding to a rise in intracellular free Ca2+ (from the control value of 315+/-23 nmol/L to 708+/-104 after the administration of hydrogen peroxide, p < 0.01), which also paralleled the elevation of end-diastolic pressure. Thus glycolytic inhibition and intracellular Ca2+ overload are independently responsible for the biphasic contractile dysfunction induced by hydrogen peroxide.
Mol Cell Biochem 2000 Jan
PMID:Role of high-energy phosphate metabolism in hydrogen peroxide-induced cardiac dysfunction. 1071 30

The rotational spectrum of the 1-cyano-3-fluoro-but-1-ene has been recorded with a pulsed-nozzle microwave Fourier transform spectrometer over the range 6-20 GHz. The frequencies were fitted to the Hamiltonian of Watson (A-reduction, I(r) representation). The resulting rotational constants are A = 7493.404(1) MHz, B = 1211.9831(2) MHz, and C = 1096.0908(1) MHz. By comparing the experimental rotational constants with those obtained by ab initio calculations, we found without ambiguity that the stable conformation for the molecule is the one with the fluorine atom lying in the C&bond;CCN plane (CF-eclipsed conformer). Copyright 2000 Academic Press.
J Mol Spectrosc 2000 Jul
PMID:Microwave Spectrum of 1-Cyano-3-fluoro-but-1-ene. 1083 63

The synthesis and NMR study (1H, 13C, and 19F) of a complete series of 4,5-substituted 1-acetyl-8-fluoronaphthalenes are reported. This data revealed a 6J(H,F) and a 5J(C,F) through space coupling between the fluorine and the methyl on the acetyl group (1H and 13C). The magnitude of this coupling constant changes depending on the nature of the substituent at C-4, the internuclear distance, and the solvent.
Spectrochim Acta A Mol Biomol Spectrosc 2000 May
PMID:Synthesis and experimental study of through-space hydrogen-fluorine and carbon-fluorine spin-spin coupling in 4,5-substituted 1-acetyl-8-fluoronaphthalenes. 1084 46

The effects of water and heavy water on conformational equilibria of fluoroacetone have been investigated via Raman spectroscopy. Additional Raman bands have been observed in the C-F stretching and the C-C-C symmetric stretching regions for the aqueous solutions. Based on enthalpy and volume differences between the conformers, these bands are assigned to the syn conformer which has hydrogen bonds between the fluorine atom and water molecules (syn' conformer). The number of H2O molecules binding to the syn' conformer is estimated to be 2.4 from the concentration dependence of the spectrum. The enthalpy and the volume differences between the cis and syn conformers in the aqueous solutions show anomalous values in comparison with those in organic solvents. We discuss these thermodynamic behaviors from the viewpoint of the hydration structures of fluoroacetone.
Spectrochim Acta A Mol Biomol Spectrosc 2000 Aug
PMID:Raman study on conformational equilibria of fluoroacetone in aqueous solutions. 1095 31

Fluoride stimulates bone cell proliferation and nodule formation in fetal rat calvarial osteoblastic cells. In addition, fluoride enhances alkaline phosphatase activity, a marker of osteoblastic differentiation, in a dose-dependent manner. The effects of fluoroalumino complex (AlFx) on cell proliferation and differentiation were markedly reduced by tyrosine kinase inhibitor; 1 mM genistein or 1 microg/ml herbimycin. It suggests that tyrosine kinase-mediated mitogenic signaling involves a series of protein-protein interactions between tyrosine-phosphorylated receptors, Shc and Grb2, resulting in an AlFx-induced mitogenic effect. The results indicate that AlFx dose-dependently enhances the tyrosine phosphorylation of the adaptor molecule Shc (p52) and its association with Grb2 in the tyrosine kinase mediated pathway. In addition, AlFx decreases the phosphorylation level of CREB without any change on the amount of CREB protein. Taken together, the results suggest that adaptor proteins, including Shc and Grb2 of the protein tyrosine kinase cascade are implicated in fluoride-induced mitogenic activity of fetal rat calvarial osteoblastic cells. Furthermore, CREB which passes signals from cAMP to transcriptional factor CRE, modulates the fluoroaluminate-induced metabolism of bone cells via a decrease of phosphorylation level.
Res Commun Mol Pathol Pharmacol 1999
PMID:Mechanism of mitogenic effect of fluoride on fetal rat osteoblastic cells: evidence for Shc, Grb2 and P-CREB-dependent pathways. 1095 25

The dynamics of agonist-stimulated opioid receptor internalization and trafficking have been difficult to study in living cells in part because the available probes were inadequate. To overcome this obstacle, six new fluorescent opioid peptides were developed. Dermorphin (DERM), deltorphin (DELT), TIPP, and endomorphin were conjugated to BODIPY TR or Alexa Fluor 488, two fluorescent dyes with distinct hydrophobic properties. In membrane binding assays the fluorescent conjugates DERM-A488 or -BTR, DELT-A488 or -BTR, and TIPP-A488 displayed good binding affinity and selectivity for mu- and delta-opioid receptor subtypes. Furthermore, the fluorescent conjugates of dermorphin and deltorphin were biologically active as demonstrated by their ability to hyperpolarize locus coeruleus neurons (DERM-A488 or -BTR) and inhibit calcium currents in NG108-15 (DELT-A488). Both of these responses were antagonized by naloxone. In conjunction with confocal fluorescent microscopy the trafficking of these fluorescent ligands was monitored in real-time. The internalization of these ligands by mu- and delta-opioid receptors was found to be naloxone-sensitive and temperature-dependent. Interestingly, once these ligands were internalized the fluorescent puncta that formed became distributed in one of two patterns. In Chinese hamster ovary cells heterologously expressing either mu- or delta-opioid receptors the intracellular puncta were concentrated in the perinuclear region of the cell, whereas they were distributed throughout the cytoplasm in cells derived from either NG108-15 or SH-SY5Y cells. In summary, we have demonstrated that these novel, fluorescent opioid peptide conjugates permit real-time visual tracking of receptor-ligand complexes, including their internalization and trafficking, in living cells.
Mol Pharmacol 2000 Dec
PMID:Binding and internalization of fluorescent opioid peptide conjugates in living cells. 1109 98

The high-resolution pure rotational spectrum of GaF has been measured using a Balle-Flygare-type Fourier transform spectrometer. Improved nuclear quadrupolar coupling constants and rotational constants have been obtained along with the first reported fluorine spin-rotation constant for gallium fluoride, C(I) ((69)Ga(19)F, v = 0) = +32.0(21) kHz. Accurate spin-rotation tensors from microwave or molecular beam spectroscopy are particularly important to NMR spectroscopists and theoreticians because these data provide information about anisotropic nuclear magnetic shielding in the absence of intermolecular effects. For quadrupolar nuclei such as gallium, the quadrupolar interaction is sufficiently large that it is very difficult to characterize shielding tensors directly via NMR spectroscopy. The experimentally determined nuclear quadrupolar coupling constants and spin-rotation constants for GaF are compared with the results of a series of high-level ab initio calculations carried out at various levels of theory with a range of basis sets. Further calculations on BF and AlF, supplemented with available experimental data for InF and TlF, allow for the investigation of trends in nuclear magnetic shielding, spin-rotation, and electric field gradient tensors in the group-13 fluorides. Calculations at the MP2/6-311++G** and MP2/6-311G(2df, 2pd) levels provide the most consistently satisfactory results in comparison with the experimental data. Copyright 2000 Academic Press.
J Mol Spectrosc 2000 Dec
PMID:Hyperfine Structure in the Rotational Spectrum of GaF: A Comparison of Experimental and Calculated Spin-Rotation and Electric Field Gradient Tensors. 1114 88


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