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1.
Eric M. Koehn 《Archives of biochemistry and biophysics》2010,493(1):96-10494
For several decades only one chemical pathway was known for the de novo biosynthesis of the essential DNA nucleotide, thymidylate. This reaction catalyzed by thyA or TYMS encoded thymidylate synthases is the last committed step in the biosynthesis of thymidylate and proceeds via the reductive methylation of uridylate. However, many microorganisms have recently been shown to produce a novel, flavin-dependent thymidylate synthase encoded by the thyX gene. Preliminary structural and mechanistic studies have shown substantial differences between these deoxyuridylate-methylating enzymes. Recently, both the chemical and kinetic mechanisms of FDTS have provided further insight into the distinctions between thyA and thyX encoded thymidylate synthases. Since FDTSs are found in several severe human pathogens their unusual mechanism offers a promising future for the development of antibiotic and antiviral drugs with little effect on human thymidylate biosynthesis. 相似文献
2.
Pedro J. N. Silva Richard K. Koehn Walter J. Diehl III Robin P. Ertl Elaine B. Winshell Mauro Santos 《Biochemical genetics》1989,27(7-8):451-467
Four samples of the musselMytilus edulis were taken between 1984 and 1987 from Stony Brook, New York, and used to study the glucose-6-phosphate isomerase (GPI) polymorphism
in this species.In vitro specific activity andin vivo flux measured in the same animals were found to be significantly correlated. A significant effect of GPI genotype on flux
was observed in one of the samples; overall, significant evidence of effect of genotype on enzyme activity was also obtained.
GPI activities of common genotypes tend to deviate less from the population mean than those of rare (frequency less than 5%)
genotypes. This suggests the possibility that rare GPI genotypes are rare as a consequence of having biochemical properties
that deviate from an optimum level and, therefore, having a lower fitness. In support of this hypothesis, we found in one
of our samples that shell length is a concave function of GPI activity with an intermediate optimum activity level.
The financial support provided to P.J.N.S. by the Luso-American Educational Commission (Fulbright Program), the Instituto
Nacional de Investigacao Científica (Portugal), and the Faculdade de Ciências da Universidade de Lisboa during several stages
of this research is gratefully acknowledged. Financial support from the Ministerio de Educatión y Ciencia (Spain) in the form
of a postdoctoral Fulbright/MEC fellowship to M.S. is also gratefully acknowledged. Research was supported by National Science
Foundation Grant BSR-8415060 to R.K.K. This is contribution No. 736 from the Program in Ecology and Evolution, State University
of New York at Stony Brook.
On leave from Departamento de Biologia Vegetal, Faculdade de Ciências, Universidade de Lisboa, Campo Grande C2, Lisboa, Portugal. 相似文献
3.
The Differential Contribution by Individual Enzymes of Glycolysis and Protein Catabolism to the Relationship between Heterozygosity and Growth Rate in the Coot Clam, Mulinia Lateralis 总被引:1,自引:1,他引:0 下载免费PDF全文
The locus-specific effects of heterozygosity upon individual growth rate were determined for 15 polymorphic enzymes among 1906 individuals from a single cohort sample of the marine bivalve Mulinia lateralis. Two measures of individual growth rate (total wet weight and shell length) were made at collection and after a period of growth in the laboratory. The correlation between heterozygosity and growth rate was independently determined for each locus using multiple linear regression, thereby providing a rank of individual locus effects; these differed significantly. The four estimated rankings of relative locus effects (initial length, initial weight, length added in the laboratory, and added weight) were not statistically different. That is, a locus with a large effect of heterozygosity on growth rate in nature had a similarly large effect on laboratory growth rate. The effect of a locus was not related to heterozygosity per se; some highly heterozygous loci had no detectable correlation with growth rate. The data contained two pairs of relatively tightly linked loci; in both cases one locus of a pair had significant effects on growth rate, while the other had no effect. Loci with large and significant correlations with growth rate synthesize enzymes which function in protein catabolism or glycolysis; heterozygosity in enzymes of the pentose shunt, redox balance, or other miscellaneous metabolic roles was not correlated with growth rate. Since the metabolic basis for the correlation is known to derive from individual differences in net energy status, particularly energetic costs of whole-body protein turnover, these data indicate that phenotypic effects (e.g., variation in growth rate) are determined by heterozygosity at the studied genes, not other linked loci. 相似文献
4.
The acid hydrolysis product of saxitoxin is shown to be decarbamoylsaxitoxin by spectral characterization and its reconversion to saxitoxin by carbamoylation. Natural and resynthesized saxitoxin are identical in chromatographic and spectral properties and in their potencies in blocking the sodium channel in squid giant axon. The hydrolysis product, decarbamoylsaxitoxin, exhibits 20% of the potency of saxitoxin in the squid axon system. These results confirm the structure of the hydrolysis product and its biological activity relative to saxitoxin. 相似文献
5.
6.
John J. Malinowski Bruce L. Grasberger Gary Trakshel Edward E. Huston Tracey M. Banks Patricia G. Brake Richard B. Ciccarelli Barry N. Jones James A. Koehn Diane Kratz Nicole Lundberg Panayiotis E. Stevis Carla T. Helaszek Mark A. Ator Angela M. Small Wood Travis Stams Byron Rubin Richard S. Alexander 《Protein science : a publication of the Protein Society》1995,4(10):2149-2155
7.
A radioimmune assay for microtubule protein, tubulin, is described, in which unknown amounts of native or denatured tubulin can be quantitated by the ability to compete with pure [125I]tubulin for rabbit antibodies produced against purified bovine brain tubulin. The assay is used to demonstrate that crude extracts of mouse brain contain negligible amounts of 30–36S tubulin oligomers under conditions where purified tubulin forms substantial amounts of such structures. Also, the particulate fraction of osmotically shocked and sonicated brain synaptosomes contains negligible tubulin antigenic activity. By contrast, soluble extracts of soybean, especially rapidly dividing regions of the plant, were found to contain significant amounts of cross-reacting material, providing further evidence for the conservative evolutionary nature of this ubiquitous and important protein. 相似文献
8.
Data from published sources were used to compare the numbers of different electrophoretic alleles of 29 monomeric and dimeric human enzymes to their respective subunit molecular weights. Only those human enzymes were considered for which the total sample sizes were in excess of 2000 individuals. Correlations between these two variables were determined within sample size ranges of 2000≤n≤3000 and 4000≤n≤5000 individuals, and separately by quaternary class. There was no statistically significant correlation observed for the smaller sample size range in monomers; however, the correlations for the larger sample size range in monomers and both ranges in dimers were significant. Since there is no relationship between subunit size and heterozygosity, the relationships are due primarily to the incidence of rare alleles. These findings demonstrate the effect of locus-specific mutation rates, expected as a consequence of variation of cistron sizes, and imply that other forces are responsible for the relative frequencies of common alleles at some of the loci. 相似文献
9.
Genetic Organization and Adaptive Response of Allozymes to Ecological Variables in FUNDULUS HETEROCLITUS 总被引:1,自引:1,他引:0 下载免费PDF全文
Populations of Fundulus heteroclitus, (Cyprinodontidae) a widespread coastal marine fish, were studied in control and artificially heated environments on the North Shore of Long Island, New York to determine (1) patterns of variation in biochemical phenotypes and (2) the extent to which this variation reflected adaptation to environmental characteristics.—Variation at three of twelve polymorphic isoenzyme loci from the warm water population was beyond the range of variation among control populations, and resembled those determined for populations living at more southern latitudes. Hence, these differences were interpreted as adaptations to warm environments. Significant differences in allele frequencies and zygotic proportions at ten of twelve isoenzyme loci were found associated with differences in environments, sexes, and/or age classes. These data strongly support the view that protein polymorphisms are adaptive.—Several observations suggested that selection acts upon multilocus phenotypes rather than upon those of single loci. Several di-locus phenotypic distributions were demonstrated to be nonrandom, and those that exhibited similar patterns of dependence over years were postulated to be maintained by selection. Highly heterozygous fish exhibited superior viability when cohorts were compared over successive years.—The consequences of the polygynous mating system in this species for maintaining genetic variation and for allowing rapid evolutionary response to a variable environment are discussed. 相似文献
10.
Scott Raymond John Koehn Zeb Tonkin Charles Todd Daniel Stoessel Graeme Hackett Justin O'Mahony Kelvin Berry Jarod Lyon Joanne Sharley Paul Moloney 《Restoration Ecology》2019,27(6):1463-1472
Globally, river degradation has decimated freshwater fish populations. To help reverse this trend in a southeastern Australia river, we used multiple restoration actions, including reintroduction of instream woody habitat, riparian revegetation, removal of a weir hindering fish movement, fencing out livestock, and controlling riparian weeds. We monitored the responses of native fish at the segment scale (20 km) and reach scale (0.3 km) over 7 years to assess the effectiveness of the different restoration strategies. Two closely related species, Murray cod Maccullochella peeli and trout cod Maccullochella macquariensis, increased at the restored segment compared with the control segment. However, inherent differences between river segments and low sample size hampered assessment of the mechanisms responsible for segment‐scale changes in fish abundance. In contrast, at the reach scale, only M. peeli abundance significantly increased in reaches supplemented with wood. These differential responses by 2 closely related fish species likely reflect species‐specific responses to increased habitat availability and enhanced longitudinal connectivity when the weir improved passage around a fishway. Changes in M. peeli abundance in segments supplemented with and without wood suggest an increase in carrying capacity and not simply a redistribution of individuals within the segment, facilitated the observed expansion. Our findings confirm the need to consider individual fish species' habitat preferences carefully when designing restoration interventions. Further, species‐specific responses to restoration actions provide waterway managers with precise strategies to target fish species for recovery and the potential to predict fish outcomes based on ecological preferences. 相似文献