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121.
The crystal structure of a colorless variant of green fluorescent protein (GFP) containing the Y66L substitution has been determined to 1.5 A. Crystallographic evidence is presented for the formation of a trapped intermediate on the pathway of chromophore maturation, where the peptide backbone of residues 65-67 has condensed to form a five-membered heterocyclic ring. The hydroxyl leaving group remains attached to the ring as confirmed by high-resolution electrospray mass spectrometry. The alpha-carbon of residue 66 exhibits trigonal planar geometry, consistent with ring oxidation by molecular oxygen. Side chain positions of surrounding residues are not perturbed, in contrast to structural results obtained for the GFPsol-S65G/Y66G variant [Barondeau, D. P., Putnam, C. D., Kassmann, C. J., Tainer, J. A., and Getzoff, E. D. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 12111-12116]. The data are in accord with a reaction pathway in which dehydration is the last of three chemical steps in GFP chromophore formation. A novel mechanism for chromophore biosynthesis is proposed: when the protein folds, the backbone condenses to form a cyclopentyl tetrahedral intermediate. In the second step, the ring is oxidized by molecular oxygen. In the third and final step, elimination of the hydroxyl leaving group as water is coupled to a proton transfer reaction that may proceed via hydrogen-bonded solvent molecules. Replacement of the aromatic Tyr66 with an aliphatic residue appears to have a profound effect on the efficiency of ring dehydration. The proposed mechanism has important implications for understanding the factors that limit the maturation rate of GFP. 相似文献
122.
Huffman JW Bushell SM Miller JR Wiley JL Martin BR 《Bioorganic & medicinal chemistry》2002,10(12):4119-4129
Three series of new cannabinoids were prepared and their affinities for the CB1 and CB2 cannabinoid recptors were determined. These are the 1-methoxy-3-(1′,1′-dimethylalkyl)-, 1-deoxy-11-hydroxy-3-(1′,1′-dimethylalkyl)- and 11-hydroxy-1-methoxy-3-(1′,1′-dimethylalkyl)-Δ8-tetrahydrocannabinols, which contain alkyl chains from dimethylethyl to dimethylheptyl appended to C-3 of the cannabinoid. All of these compounds have greater affinity for the CB2 receptor than for the CB1 receptor, however only 1-methoxy-3-(1′,1′-dimethylhexyl)-Δ8-THC (JWH-229, 6e) has effectively no affinity for the CB1 receptor (Ki=3134±110 nM) and high affinity for CB2 (Ki=18±2 nM). 相似文献
123.
124.
Risk and control of waterborne cryptosporidiosis 总被引:1,自引:0,他引:1
Cryptosporidium remains at the forefront of studies on waterborne disease transmission and abatement. The impact of environmental land use patterns which contribute animal and human waste, climatic precipitation leading to a strong association with outbreaks, and community infrastructure and water treatment are now recognized as contributing factors in the potential for waterborne spread of the protozoan. Advances in detection methodologies, including the ability to genotype various strains of this organism, have shown that human wastes are often the source of the contamination and cell culture techniques have allowed insight into the viability of the oocyst populations. Currently water treatment has focused on UV and ozone disinfection as most promising for the inactivation of this protozoan pathogen. 相似文献
125.
126.
Multiple duplications of yeast hexose transport genes in response to selection in a glucose-limited environment 总被引:11,自引:2,他引:9
When microbes evolve in a continuous, nutrient-limited environment, natural
selection can be predicted to favor genetic changes that give cells greater
access to limiting substrate. We analyzed a population of baker's yeast
that underwent 450 generations of glucose-limited growth. Relative to the
strain used as the inoculum, the predominant cell type at the end of this
experiment sustains growth at significantly lower steady-state glucose
concentrations and demonstrates markedly enhanced cell yield per mole
glucose, significantly enhanced high-affinity glucose transport, and
greater relative fitness in pairwise competition. These changes are
correlated with increased levels of mRNA hybridizing to probe generated
from the hexose transport locus HXT6. Further analysis of the evolved
strain reveals the existence of multiple tandem duplications involving two
highly similar, high- affinity hexose transport loci, HXT6 and HXT7.
Selection appears to have favored changes that result in the formation of
more than three chimeric genes derived from the upstream promoter of the
HXT7 gene and the coding sequence of HXT6. We propose a genetic mechanism
to account for these changes and speculate as to their adaptive
significance in the context of gene duplication as a common response of
microorganisms to nutrient limitation.
相似文献
127.
Acceptor specificity of the human leukocyte alpha3 fucosyltransferase: role of FucT-VII in the generation of selectin ligands 总被引:2,自引:2,他引:0
Britten CJ; van den Eijnden DH; McDowell W; Kelly VA; Witham SJ; Edbrooke MR; Bird MI; de Vries T; Smithers N 《Glycobiology》1998,8(4):321-327
The alpha3 fucosyltransferase, FucT-VII, is one of the key
glycosyltransferases involved in the biosynthesis of the sialyl Lewis X
(sLex) antigen on human leukocytes. The sialyl Lewis X antigen
(NeuAcalpha(2-3)Galbeta(1-4)[Fucalpha(1-3)]GlcNAc-R) is an essential
component of the recruitment of leukocytes to sites of inflammation,
mediating the primary interaction between circulating leukocytes and
activated endothelium. In order to characterize the enzymatic properties of
the leukocyte alpha3 fucosyltransferase FucT-VII, the enzyme has been
expressed in Trichoplusia ni insect cells. The enzyme is capable of
synthesizing both sLexand sialyl-dimeric-Lexstructures in vitro , from
3'-sialyl-lacNAc and VIM-2 structures, respectively, with only low levels
of fucose transfer observed to neutral or 3'-sulfated acceptors. Studies
using fucosylated NeuAcalpha(2-3)-(Galbeta(1- 4)GlcNAc)3-Me acceptors
demonstrate that FucT-VII is able to synthesize both di-fucosylated and
tri-fucosylated structures from mono- fucosylated precursors, but
preferentially fucosylates the distal GlcNAc within a polylactosamine
chain. Furthermore, the rate of fucosylation of the internal GlcNAc
residues is reduced once fucose has been added to the distal GlcNAc. These
results indicate that FucT-VII is capable of generating complex selectin
ligands, in vitro , however the order of fucose addition to the lactosamine
chain affects the rate of selectin ligand synthesis.
相似文献
128.
Koichi Koshimizu Hajime Ohigashi Michael A. Huffman Toshisada Nishida Hiroyuki Takasaki 《International journal of primatology》1993,14(2):345-356
Potential medicinal plants for wild chimpanzees have been studied in order to discover their physiologically active compounds. Tests of the physiological activity of 3 plant species—Vernonia amygdalina, Aspilia mossambicensis, andFicus exasperata—indicate that they contain a variety of active compounds. From one species,V. amygdalina, an antitumor agent and 2 possible antitumor promoters are identified. Furthermore, steroid glucosides were isolated as the bitter substances. These structurally new compounds are expected to exhibit a number of significant physiological activities. The chemical investigation of possible medicinal plants used by chimpanzees should be helpful in recovering naturally occurring compounds of medicinal significance for human use. 相似文献
129.
A 12-year-old female chimpanzee (Pan troglodytes schweinfurthii) of M-Group in the Mahale Mountains National Park, Tanzania was seen to rouse, capture, and eat a squirrel hiding in the
narrow hole of a tree. The kill was aided by the use of a sturdy tool modified from a branch of the same tree. This appears
to be the first reported case for chimpanzees, or any other nonhuman primate, of tool-use that directly led to the capture
of a mammalian prey species. This behavior is discussed in relation to possible factors contributing to the occurrence of
tool-use in small mammal predation especially by females to exploit a low competition meat source. 相似文献
130.