Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016632 (Fox)
 1,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The practice of vivisection is both defended as necessary to medical advancement and attacked as being symptomatic of a breakdown in society. White cites examples of people who survived critical or debilitating illnesses because of research on animals. His position is that through the use of animal experimentation cures and vaccines were found, and that research using animals must be continued to find cures for AIDS and other current, threatening illnesses. Fox contends that because of an already existing ecological breakdown, further advances in medical knowledge via animal research will not be forthcoming. He compares vivisection to terrorism and, citing the doctrine of ahisma (nonviolence), advocates the abolition of vivisection.
 ...
PMID:Contested terrain. Beastly questions. 270 39

Chloroplast fructose-1,6-bisphosphatase (FbPase) is an essential enzyme in the photosynthetic pathway of carbon dioxide fixation into sugars. The properties of the chloroplast enzyme are clearly distinct from those of cytosolic gluconeogenic FbPases. Light-dependent activation via a ferredoxin/thioredoxin system and insensitivity to inhibition by AMP are unique characteristics of the chloroplast enzyme. However, preliminary amino acid sequence data (78 residues) have demonstrated that a significant degree of amino acid sequence similarity exists between spinach chloroplast and mammalian gluconeogenic fructose-1,6-bisphosphatase [Harrsch, P.B., Kim, Y., Fox, J.L., & Marcus, F. (1985) Biochem. Biophys. Res. Commun. 133, 520-526]. In the present study, we have identified two structural features of spinach chloroplast FbPase that appear to be common to all FbPases. These include (a) the presence of a protease-sensitive area located in a region equivalent to residues 51-71 of mammalian FbPases and (b) the recognition of two conserved histidine residues, equivalent to histidines-253 and -311 of the mammalian enzymes. In addition, we have obtained sequence information accounting for more than three-fourths of the primary structure of spinach chloroplast FbPase. The high degree of homology observed between the chloroplast enzyme and gluconeogenic FbPases suggests a common evolutionary origin for all fructose-1,6-bisphosphatases in spite of their different functions and modes of regulation.
 ...
PMID:Spinach chloroplast fructose-1,6-bisphosphatase: identification of the subtilisin-sensitive region and of conserved histidines. 282 42

In 1982, we advanced a phylogeny that attributed eight alleles of the phosphoglucomutase 1 locus (PGM1) to three independent mutations in a primal allele, followed by four intragenic recombination events involving these mutants [Takahashi, N., Neel, J. V., Satoh, C., Nishizaki, J. & Masunari, N. (1982) Proc. Natl. Acad. Sci. USA 79, 6636-6640]. The recent description of a cDNA probe for this locus [Whitehouse, D. B., Putt, W., Lovegrove, J. U., Morrison, K., Hollyoake, M., Fox, M. F., Hopkinson, D. A. & Edwards, Y. H. (1992) Proc. Natl. Acad. Sci. USA 89, 411-415] now renders it possible to test the validity of this phylogeny. cDNAs of PGM1 reverse-transcribed from mRNAs obtained from Japanese individuals possessing eight different electrophoretically defined alleles (PGM1*1+, PGM1*1-, PGM1*2+, PGM1*2-, PGM1*3+, PGM1*3-, PGM1*7+, PGM1*7-) were amplified by PCR and the sequences were determined. Only three different base substitutions were identified when PGM1*1+ was taken as the reference allele, as follows: an A to T transversion at residue 265, a C to T transition at residue 723, and a T to C transition at residue 1320. The second of these substitutions creates a Bgl II restriction enzyme site and the third creates a Nla III site. At the amino acid level, these substitutions alter amino acid 67 from Lys to Met, amino acid 220 from Arg to Cys, and amino acid 419 from Tyr to His, respectively. These mutations resulted in the electrophoretic properties defining PGM1*7+, the PGM1*2+, and the PGM1*1- alleles, respectively. Subsequent intragenic recombinational events resulted in the remaining four alleles. For two of these latter alleles (PGM1*7- and PGM1*3-), more than one type of intragenic crossover can produce the allele. These findings verify the predicted phylogeny and provide a case study in the evolution of complexity at a genetic locus.
 ...
PMID:Intragenic recombination at the human phosphoglucomutase 1 locus: predictions fulfilled. 790 67

Cytochrome c peroxidase (CCP) was derivatized using aquopentaammineruthenium(II) [a5RuIIH2O] resulting in stable, covalently-linked derivatives that were purified by cation-exchange FPLC. Spectrophotometric determination of a5RuHis:heme ratios allowed identification of two derivatives containing one a5RuHis per CCP molecule. The histidine-specific reagent, diethyl pyrocarbonate (DEPC), which reacted with three histidine residues in native CCP (6, 60, 96) at pH 7, reacted with only two histidines in both a5RuHisCCP species. X-ray crystallography showed that a5Ru is coordinated to His60 in one derivative [Fox et al. (1990) J. Am. Chem. Soc. 112, 7426]; HPLC and mass spectral analysis of the tryptic peptides of the other derivative identified a peptide (MW = 1469 Da) corresponding to residues 1-12 of CCP plus a5Ru, indicating His6 as the site of modification. Mass spectral analysis of native CCP, a5RuHis60CCP, and the a5RuHis6 derivative yielded MWs of 33,536, 33,717, and 33,901 Da, respectively, revealing that a second site is ruthenated in the His6 derivative. Mass spectral analysis of a shoulder separated from the a5RuHis60CCP FPLC peak also indicated the presence of CCP with bound a5Ru (MW = 33,718 Da). Differential pulse voltammetry of this shoulder, which has negligible a5RuHis absorption, gave a peak at -68 mV (vs NHE) which is in the range expected for reduction of a5RuIII (carboxylato) complexes, as well as a peak at 42 mV due to the presence of approximately 20% a5RuHis60CCP. The extent of ruthenation at sites other than histidine was unexpected and illustrates that a5RuIIH2O is less specific for histidine than previously thought. Activity measurements and stability of enzyme intermediates were measured to further characterize the a5RuCCP species and showed that the derivatives have similar properties to native CCP.
 ...
PMID:Derivatization of yeast cytochrome c peroxidase with pentaammineruthenium(III). 819 29

Electron spin echo envelope modulation spectroscopy identified two ligand 14N interactions with the mixed-valence, Fe(II/III) diiron center of methane monooxygenase hydroxylase from Methylococcus capsulatus (Bath). Characteristic features of the spectra obtained at 9 and 10 GHz were analyzed and fit by simulation. One of the nitrogens possessed superhyperfine parameters (Aiso = 0.8 MHz, reff = 3.2 A, e2Qq = 1.8 MHz, eta = 0.35) consistent with a non-coordinating amino nitrogen of a histidine imidazole ligand to a Fe(III). The second, more strongly interacting nitrogen (Aiso = 5.0 MHz, reff = 2.2 A, e2Qq = 3.0 MHz, eta = 0.3) corresponds to the N delta directly bound to the effective Fe(II). These findings extend the previous electron nuclear double resonance results on the Methylosinus trichosporium hydroxylase (Hendrich, M.P., Fox, B.G., Andersson, K.K., Debrunner, P.G., and Lipscomb, J.D. (1992) J. Biol. Chem. 267, 261-269), which identified the N delta-Fe(II) interaction but failed to quantify its magnitude. Measurement of the linear electric field g shift of this mixed-valence species indicated that the site is charge-polarized on to one of the iron atoms, and its symmetry suggests that either charge is shifted away from the Fe-Fe axis (if gmax is defined by the Fe-Fe axis) or that gmid and gmax are perpendicular to the Fe-Fe axis (charge strongly localized at Fe(III) and axis taken as gmin).
 ...
PMID:Nuclear hyperfine coupling of nitrogen in the coordination sphere of the diiron center of methane monooxygenase hydroxylase. 820 95

Old Yellow Enzyme (OYE) binds phenolic ligands forming long wavelength (500-800 nm) charge-transfer complexes. The enzyme is reduced by NADPH, and oxygen, quinones, and alpha,beta-unsaturated aldehydes and ketones can act as electron acceptors to complete catalytic turnover. Solution of the crystal structure of OYE1 from brewer's bottom yeast (Fox, K. M., and Karplus, P. A. (1994) Structure 2, 1089-1105) made it possible to identify histidine 191 and asparagine 194 as amino acid residues that hydrogen-bond with the phenolic ligands, stabilizing the anionic form involved in charge-transfer interaction with the FMN prosthetic group. His-191 and Asn-194 are also predicted to interact with the nicotinamide ring of NADPH in the active site. Mutations of His-191 to Asn, Asn-194 to His, and a double mutation, H191N/N194H, were made of OYE1. It was not possible to isolate the N191H mutant enzyme, but the other two mutant forms had the expected effect on phenolic ligand binding, i.e. decreased binding affinity and decreased charge-transfer absorbance. Reduction of the H191N mutant enzyme by NADPH was similar to that of OYE1, but the reduction rate constant for NADH was greatly decreased. The double mutant enzyme had an increased rate constant for reduction by NADPH, but the reduction rate constant with NADH was lower by a factor of 15. The reactivity of OYE1 and the mutant enzymes with oxygen was similar, but the reactivity of 2-cyclohexenone was greatly decreased by the mutations. The crystal structures of the two mutant forms showed only minor changes from that of the wild type enzyme.
 ...
PMID:On the active site of Old Yellow Enzyme. Role of histidine 191 and asparagine 194. 983 19

On 21 July, Lord Soulsby of Swaffham Prior took office as President of the Royal Society of Medicine. He qualified mrcvs from Edinburgh in 1948 and held lectureships in Bristol and Cambridge before appointment as Professor of Parasitology in the University of Pennsylvania in 1964. There he stayed for fourteen years, returning to Cambridge in 1978 as Professor of Animal Pathology (now Emeritus). His work as a parasitologist has taken him to the USSR, Nigeria, India, Australia, South America, China and numerous countries of Europe. Earlier presidencies have included the Royal College of Veterinary Surgeons, the World Association for the Advancement of Parasitology, the Cambridge Society for Comparative Medicine, and the Comparative Medicine Section of the RSM (1993-95); he is Patron of the Fund for Replacement of Animals in Medical Experiments. He has been a consultant to international bodies including WHO, the UN Development Programme, FAO, and the International Atomic Energy Agency. Created a life peer in 1990 (now on the Opposition benches), he chaired a Select Committee on antibiotic resistance whose report appeared earlier this year. He is interviewed here by Robin Fox.
 ...
PMID:A veterinary President. Interview by Robin Fox. 1032 86

T4MOC is a 12.3 kDa soluble Rieske ferredoxin that is obligately required for electron transfer between the oxidoreductase and diiron hydroxylase components of toluene 4-monooxygenase from Pseudomonas mendocina KR1. Our preliminary 1H NMR studies of oxidized and reduced T4MOC [Markley, J. L., Xia, B., Chae, Y. K., Cheng, H., Westler, W. M., Pikus, J. D., and Fox, B. G. (1996) in Protein Structure Function Relationships (Zaidi, Z., and Smith, D., Eds.) pp 135-146, Plenum Press, London] revealed the presence of hyperfine-shifted 1H resonances whose short relaxation times made it impractical to use nuclear Overhauser effect (NOE) measurements for assignment purposes. We report here the use of selective isotopic labeling to analyze the hyperfine-shifted 1H, 2H, and 15N signals from T4MOC. Selective deuteration led to identification of signals from the four Hbeta atoms of cluster ligands C45 and C64 in the oxidized and reduced forms of T4MOC. In the reduced state, the Curie temperature dependence of the Hbeta protons corresponded to that predicted from the simple vector spin-coupling model for nuclei associated with the localized ferric site. The signal at 25.5 ppm in the 1H spectrum of reduced T4MOC was assigned on the basis of selective 2H labeling to the His Hepsilon1 atom of one of the cluster ligands (H47 or H67). This assignment was corroborated by a one bond 1H-13C correlation (at 25.39 ppm 1H and 136.11 ppm 13C) observed in spectra of [U-13C]T4MOC with a 1H-13C coupling constant of approximately 192 Hz. The carbon chemical shift and one bond coupling constant are those expected for 1Hepsilon1-13Cepsilon1 in the imidazolium ring of histidine and are inconsistent with values expected for cysteine 1Halpha-13Calpha. The His Hepsilon1 proton exhibited weak Curie temperature dependence from 283 to 303 K, contrary to the anti-Curie temperature dependence predicted from the spin coupling model for nuclei associated with the localized ferrous site. A 1H peak at -12.3 ppm was observed in spectra of reduced T4MOC; this signal was found to correspond to a hydrogen (probably in an H-bond to the cluster) that exchanged with solvent with a half-time of about 2 days in the oxidized state but with a much longer (undetectable) half-time in the reduced state. These results with T4MOC call into question certain 1H assignments recently reported on the basis of NOE measurements for the comparable Rieske ferredoxin component of an evolutionarily related alkene monooxygenase from Xanthobacter sp. Py2 [Holz, R. C., Small, F. J., and Ensign, S. A, (1997) Biochemistry 36, 14690-14696]. Selective 15N labeling was used to identify hyperfine-shifted 15N NMR signals from the backbone nitrogens of all four cluster ligands (C45, H47, C64, and H67), from the Nepsilon2 atoms of the two histidine ligands (H47 and H67), and from nonligand Gln and Ala residues (Q48 and A66) present in the cluster-binding motif of T4MOC in the oxidized and reduced states. The results indicate that the Ndelta1 of each of the two ligand histidines of T4MOC are ligated to an iron atom and reveal a pattern of H-bonding to the Rieske [2Fe-2S] center involving four (H47, Q48, A66, and H67 of T4MOC) of the five backbone amide H-bonds expected on the basis of comparison with the crystal structures of other related Rieske proteins; the fifth backbone amide (I50 of T4MOC) failed to exhibit a hyperfine shift. This anomaly may arise from the lack of an associated disulfide in T4MOC, a fundamental structural difference between the three types of Rieske proteins that may be related to functional diversity in this protein family.
 ...
PMID:Detection and classification of hyperfine-shifted 1H, 2H, and 15N resonances of the Rieske ferredoxin component of toluene 4-monooxygenase. 988 13

Aleutian mink disease parvovirus (ADV) is the etiological agent of Aleutian disease of mink. Several ADV isolates have been identified which vary in the severity of the disease they elicit. The isolate ADV-Utah replicates to high levels in mink, causing severe Aleutian disease that results in death within 6 to 8 weeks, but does not replicate in Crandell feline kidney (CrFK) cells. In contrast, ADV-G replicates in CrFK cells but does not replicate in mink. The ability of the virus to replicate in vivo is determined by virally encoded determinants contained within a defined region of the VP2 gene (M. E. Bloom, J. M. Fox, B. D. Berry, K. L. Oie, and J. B. Wolfinbarger. Virology 251:288-296, 1998). Within this region, ADV-G and ADV-Utah differ at only five amino acid residues. To determine which of these five amino acid residues comprise the in vivo replication determinant, site-directed mutagenesis was performed to individually convert the amino acid residues of ADV-G to those of ADV-Utah. A virus in which the ADV-G VP2 residue at 534, histidine (H), was converted to an aspartic acid (D) of ADV-Utah replicated in CrFK cells as efficiently as ADV-G. H534D also replicated in mink, causing transient viremia at 30 days postinfection and a strong antibody response. Animals infected with this virus developed diffuse hepatocellular microvesicular steatosis, an abnormal accumulation of intracellular fat, but did not develop classical Aleutian disease. Thus, the substitution of an aspartic acid at residue 534 for a histidine allowed replication of ADV-G in mink, but the ability to replicate was not sufficient to cause classical Aleutian disease.
 ...
PMID:Replication of Aleutian mink disease parvovirus in vivo is influenced by residues in the VP2 protein. 1048 25

William Osler was the greatest physician of his time. Specialists reading his textbooks agreed that in their own specialities he was accurate and illuminating. His grasp of dermatology was particularly striking and skin changes are prominent in five of the syndromes named after him and in at least 100 of his papers. This paper describes how his early training in dermatology under Tilbury Fox in London and Hebra in Vienna combined with his unusual personal qualities to enable him to make massive contributions to a wide variety of dermatological topics. These include smallpox, cutaneous tuberculosis, nail growth, leprosy, scleroderma, pigmentation and purpuric eruptions as well as the more obvious hereditary haemorrhagic telangiectasia, angio-neurotic oedema and Osler's nodes.
 ...
PMID:Osler and the skin. 1088 27


1 2 3 Next >>