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1.
D. G. Priest C. D. Veronee M. Mangum J. M. Bednarek M. T. Doig 《Molecular and cellular biochemistry》1982,43(2):81-87
Summary The folylpolyglutamate hydrolase activities of mouse liver, kidney, muscle and brain were examined by incorporation of methylenetetrahydrofolate polyglutamate reaction products into a stable ternary complex with tritiated fluorodeoxyuridylate and L. casei thymidylate synthetase. Complexes were separated electrophoretically on the basis of charge associated with the polyglutamyl moieties to determine distribution of chain lengths throughout the time course of the reaction. Tissue folylpolyglutamate hydrolase activities were allowed to utilize endogenous folylpolyglutamate as substrates by incubating crude tissue extracts at pH 7.4 and pH 4.5. Kidney and muscle contained relatively reactive hydrolases which were capable of generating intermediates of essentially all chain lengths from folylpentaglutamate, the predominant endogenous species. The relatively low activity in brain also gave rise to all possible intermediates. Liver contained a high concentration of methylenetetrahydrofolate but little hydrolase activity. The activity present in liver gave rise to essentially no intermediates but yielded only the monoglutamate form of the cofactor. When purified lysosomal preparations from liver and kidney were allowed to react with synthetic folylpolyglutamates, the same specificity with regard to reaction products was observed as with endogenous substrates. 相似文献
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Direct sequencing of the mitochondrial displacement loop (D-loop) of shrews
(genus Sorex) for the region between the tRNA(Pro) and the conserved
sequence block-F revealed variable numbers of 79-bp tandem repeats. These
repeats were found in all 19 individuals sequenced, representing three
subspecies and one closely related species of the masked shrew group (Sorex
cinereus cinereus, S. c. miscix, S. c. acadicus, and S. haydeni) and an
outgroup, the pygmy shrew (S. hoyi). Each specimen also possessed an
adjacent 76-bp imperfect copy of the tandem repeats. One individual was
heteroplasmic for length variants consisting of five and seven copies of
the 79-bp tandem repeat. The sequence of the repeats is conducive to the
formation of secondary structure. A termination-associated sequence is
present in each of the repeats and in a unique sequence region 5' to the
tandem array as well. Mean genetic distance between the masked shrew taxa
and the pygmy shrew was calculated separately for the unique sequence
region, one of the tandem repeats, the imperfect repeat, and these three
regions combined. The unique sequence region evolved more rapidly than the
tandem repeats or the imperfect repeat. The small genetic distance between
pairs of tandem repeats within an individual is consistent with a model of
concerted evolution. Repeats are apparently duplicated and lost at a high
rate, which tends to homogenize the tandem array. The rate of D- loop
sequence divergence between the masked and pygmy shrews is estimated to be
15%-20%/Myr, the highest rate observed in D-loops of mammals. Rapid
sequence evolution in shrews may be due either to their high metabolic rate
and short generation time or to the presence of variable numbers of tandem
repeats.
相似文献
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大鼠胼胝体内神经肽Y免疫反应阳性纤维的发育 总被引:1,自引:0,他引:1
本实验用免疫组织化学ABC法研究了大鼠胼胝体内神经肽Y免疫反应阳性(NPY-IR)纤维的生后发育。结果发现,许多NPY-IR纤维在大鼠出生时便存在于胼胝体内。NPY-IR胼胝体纤维的密度在生后1周内继续逐渐增高,在第2周内达到最高峰。之后,NPY-IR胼胝体纤维的密度逐渐下降,至第3周末时接近成年时的水平,即仅有少量NPY-IR纤维存在于胼胝体内。这些结果提示在大鼠早期生后发育过程中许多NPY-IR胼胝体纤维是暂时性的,其作用可能与大脑皮质的机能发育有关。 相似文献
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It is widely believed that the dominant force opposing protein folding is the entropic cost of restricting internal rotations. The energetic changes from restricting side-chain torsional motion are more complex than simply a loss of conformational entropy, however. A second force opposing protein folding arises when a side-chain in the folded state is not in its lowest-energy rotamer, giving rotameric strain. chi strain energy results from a dihedral angle being shifted from the most stable conformation of a rotamer when a protein folds. We calculated the energy of a side-chain as a function of its dihedral angles in a poly(Ala) helix. Using these energy profiles, we quantify conformational entropy, rotameric strain energy and chi strain energy for all 17 amino acid residues with side-chains in alpha-helices. We can calculate these terms for any amino acid in a helix interior in a protein, as a function of its side-chain dihedral angles, and have implemented this algorithm on a web page. The mean change in rotameric strain energy on folding is 0.42 kcal mol-1 per residue and the mean chi strain energy is 0.64 kcal mol-1 per residue. Loss of conformational entropy opposes folding by a mean of 1.1 kcal mol-1 per residue, and the mean total force opposing restricting a side-chain into a helix is 2.2 kcal mol-1. Conformational entropy estimates alone therefore greatly underestimate the forces opposing protein folding. The introduction of strain when a protein folds should not be neglected when attempting to quantify the balance of forces affecting protein stability. Consideration of rotameric strain energy may help the use of rotamer libraries in protein design and rationalise the effects of mutations where side-chain conformations change. 相似文献
9.
Microscale processing techniques would be a useful tool for the rapid and efficient collection of biotransformation kinetic data as a basis for bioprocess design. Automated liquid handling systems can reduce labor intensity while the small scale reduces the demand for scarce materials such as substrate, product, and biocatalyst. Here we illustrate this concept by establishing the use of several microwell formats (96-round, 96-deep square and 24-round well microtiter plates) for quantification of the kinetics of the E. coli TOP10 [pQR239] resting cell catalyzed Baeyer-Villiger oxidation of bicyclo[3.2.0]hept-2en-6-one using glycerol as a source of reducing power. By increasing the biocatalyst concentration until the biotransformation rate was oxygen mass-transfer limited we can ensure that kinetic data collected are in the region away from oxygen limitation. Using a 96-round well plate the effect of substrate (bicyclo[3.2.0]hept-2en-6-one) concentration on the volumetric CHMO activity was examined and compared to data collected from 1.5-L stirred-tank experiments. The phenomenon and magnitude of substrate inhibition, observed at the larger scale, was accurately reproduced in the microwell format. We have used this as an illustrative example to demonstrate that under adequately defined conditions, automated microscale processing technologies can be used for the collection of quantitative kinetic data. Additionally, by using the experimentally determined stoichiometry for product formation and glycerol oxidation, we have estimated the maximum oxygen transfer rates as a function of well geometry and agitation rate. Oxygen-transfer rates with an upper limit of between 33 mmol. L(-1). h(-1) (based solely on product formation) and 390 mmol. L(-1). h(-1) (based on product formation and glycerol oxidation) were achieved using a 96-square well format plate shaken at 1300 rpm operated with a static surface area to volume ratio of 320 m(2). m(-3). 相似文献
10.
Black AP Bhayani H Ryder CA Pugh MT Gardner-Medwin JM Southwood TR 《Arthritis research & therapy》2003,5(5):R277-R284
The aim of this research was to determine whether all memory T cells have the same propensity to migrate to the joint in patients
with juvenile idiopathic arthritis. Paired synovial fluid and peripheral blood mononuclear cell proliferative responses to
a panel of antigens were measured and the results correlated with a detailed set of laboratory and clinical data from 39 patients
with juvenile idiopathic arthritis. Two distinct patterns of proliferative response were found in the majority of patients:
a diverse pattern, in which synovial fluid responses were greater than peripheral blood responses for all antigens tested;
and a restricted pattern, in which peripheral blood responses to some antigens were more vigorous than those in the synovial
fluid compartment. The diverse pattern was generally found in patients with a high acute phase response, whereas patients
without elevated acute phase proteins were more likely to demonstrate a restricted pattern. We propose that an association
between the synovial fluid T cell repertoire and the acute phase response suggests that proinflammatory cytokines may influence
recruitment of memory T cells to an inflammatory site, independent of their antigen specificity. Additionally, increased responses
to enteric bacteria and the presence of αEβ7 T cells in synovial fluid may reflect accumulation of gut associated T cells
in the synovial compartment, even in the absence of an elevated acute phase response. This is the first report of an association
between the acute phase response and the T cell population recruited to an inflammatory site. 相似文献