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261.
262.
Summary The ability of time-averaged restrained molecular dynamics (TARMD) to escape local low-energy conformations and explore conformational space is compared with conventional simulated-annealing methods. Practical suggestions are offered for performing TARMD calculations with ligand-receptor systems, and are illustrated for the complex of the immunosuppressant FK506 bound to Q50R,A95H,K98I triple mutant FKBP-13. The structure of 13C-labeled FK506 bound to triple-mutant FKBP-13 was determined using a set of 87 NOE distance restraints derived from HSQC-NOESY experiments. TARMD was found to be superior to conventional simulated-annealing methods, and produced structures that were conformationally similar to FK506 bound to wild-type FKBP-12. The individual and combined effects of varying the NOE restraint force constant, using an explicit model for the protein binding pocket, and starting the calculations from different ligand conformations were explored in detail.Abbreviations DG
distance geometry
- dmFKBP-12
double-mutant (R42K,H87V) FKBP-12
- FKBP-12
FK506-binding protein (12 kDa)
- FKBP-13
FK506-binding protein (13 kDa)
- HSQC
heteronuclear single-quantum coherence
- KNOE
force constant (penalty) for NOE-derived distance restraints
- MD
molecular dynamics
- NOE
nuclear Overhauser effect
- SA
simulated annealing
- TARMD
molecular dynamics with time-averaged restraints
- tmFKBP-13
triple-mutant (Q50R,A95H,K98I) FKBP-13
- wtFKBP-12
wild-type FKBP-12 相似文献
263.
Anthony L. Moore Ann L. Umbach James N. Siedow 《Journal of bioenergetics and biomembranes》1995,27(4):367-377
A major characteristic of plant mitochondria is the presence of a cyanide-insensitive alternative oxidase which catalyzes the reduction of oxygen to water. Current information on the properties of the oxidase is reviewed. Conserved amino acid motifs have been identified which suggest the presence of a hydroxo-bridged di-iron center in the active site of the alternative oxidase. On the basis of sequence comparison with other di-iron center proteins, a structural model for the active site of the alternative oxidase has been developed that has strong similarity to that of methane monoxygenase. Evidence is presented to suggest that the alternative oxidase of plant mitochondria is the newest member of the class II group of di-iron center proteins. 相似文献
264.
A human monoclonal antibody to a complex epitope in the V3 region of gp120 of human immunodeficiency virus type 1 has broad reactivity within and outside clade B. 总被引:21,自引:18,他引:3 下载免费PDF全文
J P Moore A Trkola B Korber L J Boots J A Kessler nd F E McCutchan J Mascola D D Ho J Robinson A J Conley 《Journal of virology》1995,69(1):122-130
We have used virus neutralization and antibody-binding techniques to define the epitope for a human monoclonal antibody, designated 19b, within the V3 region of the gp120 surface glycoprotein of human immunodeficiency virus type 1. Unusually, the 19b epitope encompasses residues on both flanks of the V3 loop. However, 19b binding to gp120 is independent of sequences at the crown of the V3 loop, provided that they are compatible with the formation of a type II beta turn that is presumably necessary to juxtapose the antigenic residues on the V3 flanks. By comparing the V3 sequences of virus gp120s able and unable to bind 19b, we were able to define the canonical 19b epitope as -I----G--FY-T, where residues at the positions indicated by the gaps do not contribute directly to the 19b-binding site. A few conservative substitutions at the more critical residues are also compatible with 19b binding. Inspection of V3 sequences in the human immunodeficiency virus database indicated that the canonical 19b epitope is well conserved among isolates from the North American-European clade B and also among clade E isolates from Thailand and clade F isolates from Brazil. A minority of gp120s from clades A and C also possess the 19b epitope. Consistent with the theoretical predictions of its cross-clade reactivity, 19b was found to bind to gp120s from clades A, B, C, E, and F in immunoassays. However, 19b was not able to reduce the infectivity of primary viruses from clades A, E, and F that were predicted to possess the 19b epitope and only modestly reduced the infectivity of a clade C virus at low input virus concentrations. Cross-clade neutralization via V3-directed antibodies may, therefore, be difficult, even if the antibodies show broad reactivities in binding assays and the viruses theoretically possess the relevant binding site. 相似文献
265.
Integration of the Saccharomyces cerevisiae retrotransposon Ty1 requires the element-encoded integrase (IN) protein, which is a component of cytoplasmic virus-like particles (VLPs). Using purified recombinant Ty1 IN and an oligonucleotide integration assay based on Ty1 long terminal repeat sequences, we have compared IN activity on substrates having either wild-type or altered donor ends. IN showed a marked preference for blunt-end substrates terminating in an A:T pair over substrates ending in a G:C pair or a 3' dideoxyadenosine. VLP activity on representative substrates also showed preference for donor strands which have an adenosine terminus. Staggered-end substrates showed little activity when nucleotides were removed from the end of the wild-type donor strand, but removal of one nucleotide from the complementary strand did not significantly diminish activity. Removal of additional nucleotides from the complementary strand reduced activity to minimal detection levels. These results suggest that the sequence specificity of Ty1 IN is not stringent in vitro. The absence of Ty1 IN-mediated 3' dinucleotide cleavage, a characteristic of retroviral integrases, was demonstrated by using selected substrates. In addition to the forward reaction, both recombinant IN and VLP-associated IN carry out the reverse disintegration reaction with long terminal repeat-based dumbbell substrates. Disintegration activity exhibits sequence preferences similar to those observed for the forward reaction. 相似文献
266.
Six cDNAs representing unique cold-induced sequences have been cloned from the hardy citrus relative Poncirus trifoliata. Among these, pBCORc115 and pBCORc119 were found to belong to the same gene family. Sequencing data indicated that pBCORc115 and pBCORc119 each contained an open reading frame, coding for a 19.8 kDa protein (COR19) and a smaller 11.4 kDa protein (COR11) respectively. Inspection of the deduced amino acid sequences revealed three large repeats in COR19, but only one was present in the COR11. Two elements: a Q-clustered tract and a K-rich motif were identified in each repeat. The K-rich motifs were similar to those of cotton D-11 and Group 2 LEA proteins. A Serine-cluster, a common feature in many Group 2 LEA-like proteins, was also found in these proteins, but it was in an unusual position at the carboxy-terminus. A bipartite motif of basic residues, similar to known nuclear targeting sequences, was also present in COR19 and COR11, suggesting that members of this protein family may have a nuclear targeting function. The expression of COR19 mRNA in response to cold acclimation, drought, flooding, and salinization was examined. COR19 expression in leaf tissue was induced in response to cold acclimation, but repressed during drought and flooding stress. 相似文献
267.
Modern methods of analysis are enabling researchers to study natural selection at a new level of detail. Multivariate statistical techniques can Identify specific targets of selection and provide parameter estimates that fit into equations for evolutionary change. A more Intuitive understanding of the form of selection can be provided through graphical representation of selection surfaces. Combinations of quantitative and visual analyses are providing researchers with new insights into the details of natural selection in the wild. 相似文献
268.
Identification of alcaligin as the siderophore produced by Bordetella pertussis and B. bronchiseptica. 总被引:6,自引:5,他引:1 下载免费PDF全文
C H Moore L A Foster D G Gerbig Jr D W Dyer B W Gibson 《Journal of bacteriology》1995,177(4):1116-1118
The siderophores produced by iron-starved Bordetella pertussis and B. bronchiseptica were purified and were found to be identical. Using mass spectrometry and proton nuclear magnetic resonance, we determined that the siderophore produced by these organisms was identical to alcaligin, a siderophore produced by Alcaligenes denitrificans. 相似文献
269.
David A. Flemer Roman S. Stanley Barbara F. Ruth Charles M. Bundrick Paul H. Moody James C. Moore 《Hydrobiologia》1995,308(2):85-101
Two six-week laboratory experiments were conducted to evaluate effects of pesticides and microcosm size on benthic estuarine
macroinvertebrate recolonization. Sediments fortified with the pesticides (fenvalerate: controls, 5 (low) and 50 μg g−1 wet sediment (high); endosulfan: controls, 1 (low) and 10 μg g−1 wet sediment (high)) were fine-grained, organically rich (approximately 3.5% organic carbon and 22% dry weight) material.
Relative dominance of the four most abundant taxa in both experiments was consistent among treatments with few exceptions.
The amphipod,Corophium acherusicum, dominated abundance in both experiments.
In the fenvalerate experiment, large trays (400 cm2) contained significantly (p<0.05) more total number of taxa (TNT) than small microcosms (144 cm2) but tray size was not significantly related to total number of organisms (TNO). When size was adjusted to a common unit
area, small trays contained significantly more TNO than large containers. Adjusted abundance of small trays was 2.5 times
that of large containers; a ratio close to that of microcosm sizes (i.e., 2.8). This result suggests that larval supply may have been inadequate to ‘aturate’ the available sediment in large containers.
Fenvalerate significantly reduced abundance in the high treatment compared to both controls and low treatment but low treatment
was not significantly different from controls. The amphipod,Corophium acherusicum, accounted for most of the decrease in abundance in response to fenvalerate. The holothruroid,Leptosynpta sp. and the polychaete,Mediomastus ambiseta, increased in abundance significantly with increased concentration of fenvalerate.
Combined effects of actual microcosm size and concentration of endosulfan were not significant for TNO or TNT. As in the fenvalerate
experiment, adjusted abundance of small microcosms was 2.6 times that of large trays which approximated the ratio of unit
area between microcosm sizes. Abundance of a few taxa responded significantly to adjusted and unadjusted unit area. Abundance
of the tunicate,Molgula manhattensis, increased significantly with increased concentration of endosulfan. Abundance was affected by sample location (e.g., interiorvs exterior cores) within microcosms. Abundance adjusted to unit area resulted in significantly greater TNO in externalvs internal cores. This has importance for sequential sub-sampling of microcosms to determine temporal dynamics.
Statistically significant effects were measured in benthic community structure associated with microcosm size; however, the
magnitude was relatively small. There appears to be no major biological reason to select one microcosm size over the other
for screening for contaminant effects. Where feasible, the small trays provide savings in sample preparation and analysis,
allow more replicates where laboratory space is limiting and generate less chemical waste. These benefits may be off-set by
less ‘artifacts’ associated with edge effects of larger microcosms and the need for a larger mass of sediment to accommodate
additional analytical requirements (e.g., thin vertical surficial samples to refine contaminant exposure at the sediment/water
interface). 相似文献
270.