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51.
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53.
A modular treatment of molecular traffic through the active site of cholinesterase 总被引:1,自引:0,他引:1 下载免费PDF全文
We present a model for the molecular traffic of ligands, substrates, and products through the active site of cholinesterases (ChEs). First, we describe a common treatment of the diffusion to a buried active site of cationic and neutral species. We then explain the specificity of ChEs for cationic ligands and substrates by introducing two additional components to this common treatment. The first module is a surface trap for cationic species at the entrance to the active-site gorge that operates through local, short-range electrostatic interactions and is independent of ionic strength. The second module is an ionic-strength-dependent steering mechanism generated by long-range electrostatic interactions arising from the overall distribution of charges in ChEs. Our calculations show that diffusion of charged ligands relative to neutral isosteric analogs is enhanced approximately 10-fold by the surface trap, while electrostatic steering contributes only a 1.5- to 2-fold rate enhancement at physiological salt concentration. We model clearance of cationic products from the active-site gorge as analogous to the escape of a particle from a one-dimensional well in the presence of a linear electrostatic potential. We evaluate the potential inside the gorge and provide evidence that while contributing to the steering of cationic species toward the active site, it does not appreciably retard their clearance. This optimal fine-tuning of global and local electrostatic interactions endows ChEs with maximum catalytic efficiency and specificity for a positively charged substrate, while at the same time not hindering clearance of the positively charged products. 相似文献
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55.
Cell-to-cell transfer of glial proteins to the squid giant axon: The glia- neuron protein transfer hypothesis 下载免费PDF全文
The hypothesis that glial cells synthesize proteins which are transferred to adjacent neurons was evaluated in the giant fiber of the squid (Loligo pealei). When giant fibers are separated from their neuron cell bodies and incubated in the presence of radioactive amino acids, labeled proteins appear in the glial cells and axoplasm. Labeled axonal proteins were detected by three methods: extrusion of the axoplasm from the giant fiber, autoradiography, and perfusion of the giant fiber. This protein synthesis is completely inhibited by puromycin but is not affected by chloramphenicol. The following evidence indicates that the labeled axonal proteins are not synthesized within the axon itself. (a) The axon does not contain a significant amount of ribosomes or ribosomal RNA. (b) Isolated axoplasm did not incorporate [(3)H]leucine into proteins. (c) Injection of Rnase into the giant axon did not reduce the appearance of newly synthesized proteins in the axoplasm of the giant fiber. These findings, coupled with other evidence, have led us to conclude that the adaxonal glial cells synthesize a class of proteins which are transferred to the giant axon. Analysis of the kinetics of this phenomenon indicates that some proteins are transferred to the axon within minutes of their synthesis in the glial cells. One or more of the steps in the transfer process appear to involve Ca++, since replacement of extracellular Ca++ by either Mg++ or Co++ significantly reduces the appearance of labeled proteins in the axon. A substantial fraction of newly synthesized glial proteins, possibly as much as 40 percent, are transferred to the giant axon. These proteins are heterogeneous and range in size from 12,000 to greater than 200,000 daltons. Comparisons of the amount of amino acid incorporation in glia cells and neuron cell bodies raise the possibility that the adaxonal glial cells may provide an important source of axonal proteins which is supplemental to that provided by axonal transport from the cell body. These findings are discussed with reference to a possible trophic effect of glia on neurons and metabolic cooperation between adaxonal glia and the axon. 相似文献
56.
Esther Heikens Masja Leendertse Lucas M Wijnands Miranda van Luit-Asbroek Marc JM Bonten Tom van der Poll Rob JL Willems 《BMC microbiology》2009,9(1):19-7
Background
Enterococcus faecium has globally emerged as a cause of hospital-acquired infections with high colonization rates in hospitalized patients. The enterococcal surface protein Esp, identified as a potential virulence factor, is specifically linked to nosocomial clonal lineages that are genetically distinct from indigenous E. faecium strains. To investigate whether Esp facilitates bacterial adherence and intestinal colonization of E. faecium, we used human colorectal adenocarcinoma cells (Caco-2 cells) and an experimental colonization model in mice. 相似文献57.
Two distinct conformational states define the interaction of human RAD51‐ATP with single‐stranded DNA 下载免费PDF全文
Andrea Candelli Edwige B Garcin Mauro Modesti Luca Pellegrini Gijs JL Wuite Erwin JG Peterman 《The EMBO journal》2018,37(7)
An essential mechanism for repairing DNA double‐strand breaks is homologous recombination (HR). One of its core catalysts is human RAD51 (hRAD51), which assembles as a helical nucleoprotein filament on single‐stranded DNA, promoting DNA‐strand exchange. Here, we study the interaction of hRAD51 with single‐stranded DNA using a single‐molecule approach. We show that ATP‐bound hRAD51 filaments can exist in two different states with different contour lengths and with a free‐energy difference of ~4 kBT per hRAD51 monomer. Upon ATP hydrolysis, the filaments convert into a disassembly‐competent ADP‐bound configuration. In agreement with the single‐molecule analysis, we demonstrate the presence of two distinct protomer interfaces in the crystal structure of a hRAD51‐ATP filament, providing a structural basis for the two conformational states of the filament. Together, our findings provide evidence that hRAD51‐ATP filaments can exist in two interconvertible conformational states, which might be functionally relevant for DNA homology recognition and strand exchange. 相似文献
58.
Chimpanzee fetal G gamma and A gamma globin gene nucleotide sequences provide further evidence of gene conversions in hominine evolution 总被引:5,自引:0,他引:5
The fetal globin genes G gamma and A gamma from one chromosome of a
chimpanzee (Pan troglodytes) were sequenced and found to be closely similar
to the corresponding genes of man and the gorilla. These genes contain
identical promoter and termination signals and have exons 1 and 2 separated
by the conserved short intron 1 (122 bp) and exons 2 and 3 separated by the
more rapidly evolving, larger intron 2 (893 bp and 887 bp in chimpanzee G
gamma and A gamma, respectively). Each intron 2 has a stretch of simple
sequence DNA (TG)n serving possibly as a "hot spot" for recombination. The
two chimpanzee genes encode polypeptide chains that differ only at position
136 (glycine in G gamma and alanine in A gamma) and that are identical to
the corresponding human chains, which have aspartic acid at position 73 and
lysine at 104 in contrast to glycine and arginine at these respective
positions of the gorilla A gamma chain. Phylogenetic analysis by the
parsimony method revealed four silent (synonymous) base substitutions in
evolutionary descent of the chimpanzee G gamma and A gamma codons and none
in the human and gorilla codons. These Homininae (Pan, Homo, Gorilla)
coding sequences evolved at one-tenth the average mammalian rate for
nonsynonymous and one-fourth that for synonymous substitutions. Three
sequence regions that were affected by gene conversions between chimpanzee
G gamma and A gamma loci were identified: one extended 3' of the hot spot
with G gamma replaced by the A gamma sequence, another extended 5' of the
hot spot with A gamma replaced by G gamma, and the third conversion
extended from the 5' flanking to the 5' end of intron 2, with G gamma
replaced here by the A gamma sequence. A conversion similar to this third
one has occurred independently in the descent of the gorilla genes. The
four previously identified conversions, labeled C1-C4 (Scott et al. 1984),
were substantiated with the addition of the chimpanzee genes to our
analysis (C1 being shared by all three hominines and C2, C3, and C4 being
found only in humans). Thus, the fetal genes from all three of these
hominine species have been active in gene conversions during the descent of
each species.
相似文献
59.
Nonglucosylated oligosaccharides are transferred to protein in MI8-5 Chinese hamster ovary cells 总被引:1,自引:2,他引:1
A CHO mutant MI8-5 was found to synthesize Man9-GlcNAc2-P-P-dolichol rather
than Glc3Man9GlcNAc2-P-P-dolichol as the oligosaccharide-lipid intermediate
in N-glycosylation of proteins. MI8-5 cells were incubated with labeled
mevalonate, and the prenol was found to be dolichol. The mannose-labeled
oligosaccharide released from oligosaccharide-lipid of MI8-5 cells was
analyzed by HPLC and alpha-mannosidase treatment, and the data were
consistent with a structure of Man9GlcNAc2. In addition, MI8-5 cells did
not incorporate radioactivity into oligosaccharide- lipid during an
incubation with tritiated galactose, again consistent with MI8-5 cells
synthesizing an unglucosylated oligosaccharide-lipid. MI8-5 cells had
parental levels of glucosylphosphoryldolichol synthase activity. However,
in two different assays, MI8-5 cells lacked dolichol-
P-Glc:Man9GlcNAc2-P-P-dolichol glucosyltransferase activity. MI8-5 cells
were found to synthesize glucosylated oligosaccharide after they were
transfected with Saccharomyces cerevisiae ALG 6, the gene for
dolichol-P-Glc:Man9GlcNAc2-P-P-dolichol glucosyltransferase. MI8-5 cells
were found to incorporate mannose into protein 2-fold slower than parental
cells and to approximately a 2-fold lesser extent.
相似文献
60.