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991.
Srinivasulu S Acharya AS Prabhakaran M Fabry ME Alami R Fiering SN Bouhasirra EE Nagel RL 《The protein journal》2007,26(8):523-532
Recombinant α-Savaria globin (αS49R) was assembled with βS chains by the alloplex intermediate pathway to generate tetrameric rHbS-Sarvaria (α2S49Rβ2E6V) that exhibited normal O2 affinity and co-operatively at pH 7.4. Allosteric effectors, 2,3-DPG, L35, and NaCl increased O2 affinity by 15%. Bohr effects were similar for rHbS-Savaria and HbS (0.38 ± 0.025 vs. 0.46 ± 0.03, respectively). The CSAT of HbS increased from 16.7 ± 0.8 to 27.0 ± 1.0 g/dL. Co-polymerization demonstrated inhibition predominantly by the Cis-dimer.
Molecular modeling indicated that the positive charge at α-49 generated a strong anion-binding site and reduced flexibility
of the CD-region by restricting movement in the E and F helices. The molecular distance between Arg-49 and Asn-78 in the neighboring
double strand decreased, and electrostatic repulsion between the inter-double strands increased, resulting in inhibition of
polymerization. The Savaria mutation may be useful for the design of super-inhibitory α-chains and gene therapy of sickle
cell anemia. 相似文献
992.
A mixture of 4-chloro-1-butanol and 2,2,2-Trifluoroethanol (TFE) has been used to generate Molten globule (MG) state of structurally
homologous but functionally different proteins bovine α-lactalbumin and hen egg-white lysozyme. The thermal denaturation was
done using UV–Visible spectroscopy. From UV–Visible profile, thermal transition was not observed beyond a particular concentration.
There was an indication of molten globule state in case of α-lactalbumin from circular dichroism experiments. By intrinsic
tryptophan fluorescence, acrylamide and potassium iodide quenching, 8-anilino-naphthalene sulfonic acid (ANS) binding and
energy transfer studies the presence of molten globule state was confirmed. Quantitative characterization of MG state and
determining the binding thermodynamics of ANS to the MG state was done using Isothermal Titration Calorimetry (ITC). Results
show that α-lactalbumin exists in MG state at a particular concentration but lysozyme does not show features of MG state. 相似文献
993.
3D-QSAR studies of Dipeptidyl peptidase IV inhibitors using a docking based alignment 总被引:1,自引:0,他引:1
Dipeptidyl peptidase IV (DPP-IV) deactivates the incretin hormones GLP-1 and GIP by cleaving the penultimate proline or alanine
from the N-terminal (P1-position) of the peptide. Inhibition of this enzyme will prevent the degradation of the incretin hormones
and maintain glucose homeostasis; this makes it an attractive target for the development of drugs for diabetes. This paper
reports 3D-QSAR analysis of several DPP-IV inhibitors, which were aligned by the receptor-based technique. The conformation
of the molecules in the active site was obtained through docking methods. The QSAR models were generated on two training sets
composed of 74 and 25 molecules which included phenylalanine, thiazolidine, and fluorinated pyrrolidine analogs. The 3D-QSAR
models are robust with statistically significant r2, q2, and values. The CoMFA and CoMSIA models were used to design some new inhibitors with several fold higher binding affinity.
Figure The CoMFA contours around molecule D1T155 (a) steric contours - favored (green); disfavored (yellow) (b) electrostatic contours
- electropositive (blue); electronegative (red) 相似文献
994.
The recently introduced multipole approach for computing the molecular electrostatic potential (MEP) within the semiempirical
neglect of diatomic differential overlap (NDDO) framework [Horn AHC, Lin Jr-H., Clark T (2005) Theor Chem Acc 114:159–168] has been used to obtain atomic charges of nearly ab initio quality by scaling the semiempirical
MEP. The parameterization set comprised a total of 797 compounds and included not only the newly parameterized AM1* elements
Al, Si, P, S, Cl, Ti, Zr, and Mo but also the standard AM1 elements H, C, N, O and F. For comparison, the ZDO-approximated
MEP was also calculated analytically in the spd-basis. For the AM1*-optimized structures, single-point calculations at the B3LYP, HF and MP2 levels with the 6-31G(d) and
LanL2DZP basis sets were performed to obtain the MEP. The regression analysis of all 12 combinations of semiempirical and
ab initio MEP data yielded correlation coefficients of at least 0.99 in all cases. Scaling the analytical and multipole-derived
semiempirical MEP by the regression coefficients yielded mean unsigned errors below 2.6 and 1.9 kcal mol−1, respectively. Subsequently, for 22 drug molecules from the World Drug Index, atomic charges were computed according to the
RESP procedure using XX/6-31G(d) (XX=B3LYP, HF, MP2) and scaled AM1* multipole MEP; the correlation coefficients obtained
are 0.83, 0.85 and 0.83, respectively. Figure: Schematic representation of the atomic charge generation: The molecular electrostatic potential (MEP) is calculated using
the AM1* Hamiltonian; then the semiempirical MEP is scaled to DFT or ab initio level, and atomic charges are generated subsequently
by the restraint electrostatic potential (RESP) fit method.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorized users.
Proceedings of “Modeling Interactions in Biomolecules II”, Prague, September 5th–9th, 2005. 相似文献
995.
Debasish Haldar Arindam Banerjee 《International journal of peptide research and therapeutics》2007,13(3):439-446
The terminally protected peptide Boc-Leu-Val-Phe-Phe-Ala-OMe bearing sequence similarity with the central hydrophobic cluster
(CHC) of Alzheimer’s Aβ17–21 peptide self-assembles to produce amyloid-like straight unbranched fibrils from organic solvents. The fibrils readily bind
with a physiological dye Congo red (CR) and exhibits green gold birefringence under polarized light, a characteristic feature
of amyloid plaque obtained from many neurodegenerative diseases. FTIR spectroscopy and in silico energy minimization study shed some light on the antiparallel supramolecular β-sheet aggregation of the peptide. 相似文献
996.
Ghulam Jilani Abida Akram Raja M. Ali Fauzia Y. Hafeez Imran H. Shamsi Arshad N. Chaudhry Abid G. Chaudhry 《Annals of microbiology》2007,57(2):177-184
Field experiment was conducted on fodder maize to explore the potential of integrated use of chemical, organic and biofertilizers for improving maize growth, beneficial microflora in the rhizosphere and the economic returns. The treatments were designed to make comparison of NPK fertilizer with different combinations of half dose of NP with organic and biofertilizers viz. biological potassium fertilizer (BPF), Biopower, effective microorganisms (EM) and green force compost (GFC). Data reflected maximum crop growth in terms of plant height, leaf area and fresh biomass with the treatment of full NPK; and it was followed by BPF+full NP. The highest uptake of NPK nutrients by crop was recorded as: N under half NP+Biopower; P in BPF+full NP; and K from full NPK. The rhizosphere microflora enumeration revealed that Biopower+EM applied along with half dose of GFC soil conditioner (SC) or NP fertilizer gave the highest count of N-fixing bacteria (Azotobacter, Azospirillum, Azoarcus andZoogloea). Regarding the P-solubilizing bacteria,Bacillus was having maximum population with Biopower+BPF+half NP, andPseudomonas under Biopower+EM+half NP treatment. It was concluded that integration of half dose of NP fertilizer with Biopower+BPF / EM can give similar crop yield as with full rate of NP fertilizer; and through reduced use of fertilizers the production cost is minimized and the net return maximized. However, the integration of half dose of NP fertilizer with biofertilizers and compost did not give maize fodder growth and yield comparable to that from full dose of NPK fertilizers. 相似文献
997.
Streptoverticillium kashmirense AF1 with the ability to degrade a natural polymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) was isolated from municipal sewage sludge by soil burial technique. The PHBV film was degraded by the action of extracellular enzymes secreted by the microorganisms. Degradation of PHBV was evident by the formation of clear zones of hydrolysis on the polymer containing mineral salt agar plates. The extent of PHBV degradation increased up to 30 days of incubation. Maximum production of PHBV depolymerase was observed both at pH 8 and pH 7, 45 °C, 1% substrate concentration and in the presence of lactose as an additional carbon source. Two types of extracellular PHBV depolymerases were purified fromS. kashmirense AF1 by gel permeation chromatography using Sephadex G-75. The molecular weights of the two proteins were found to be 35 and 45 kDa approximately, as determined by SDS-PAGE. The results of the Sturm test also showed more CO2 production as a result of PHBV degradation, in the test as compared to control. The present findings indicated the degradation capabilities ofS. kashmirense AF1. 相似文献
998.
Ljiljana Vapa Mihajla Djan Dragana Obreht Milos Beukovic Milan Vapa 《European Journal of Wildlife Research》2007,53(1):52-54
The pheasant breeds are widely used for restocking of natural populations depleted by hunting. The pheasant population number
decline was detected during the 1970s in many hunting areas of Europe. One of its possible reasons might be the loss of adaptability
in populations originating from breeding stations, which was caused by inbreeding depression. The aim of this paper was the
analysis of genetic variability in pheasant populations from three breeding stations in Vojvodina province (Serbia) by means
of allozyme diversity detection. The allozyme variability analysis of pheasants from all three breeding stations revealed
polymorphisms at nine loci: Ldh-1, Mor-1, Mor-2, Es-1, Mod-2, Pgd, Gpi-2, Odh, and Sod. The analysis of individuals from three different breeding stations showed mean values of observed heterozygosity of H
o=0.137, polymorphism P
95%=30%, and H/P ratio H/P=0.430, which indicate a normal level of genetic variability for bird populations. Comparative analysis of three pheasant
populations showed a high level of interpopulation differentiation. 相似文献
999.
Distribution of haplotypes and microsatellite alleles among Asian elephants (<Emphasis Type="Italic">Elephas maximus</Emphasis>) in Thailand 总被引:1,自引:1,他引:0
Joerns Fickel Dietmar Lieckfeldt Parntep Ratanakorn Christian Pitra 《European Journal of Wildlife Research》2007,53(4):298-303
Habitat fragmentation often promotes increased inbreeding depression due to interrupted gene flow between populations. In
this study, we demonstrate that Asian elephants most likely also suffer from outbreeding depression due to cryptic speciation.
We analysed mitochondrial and nuclear DNA loci from 78 Asian elephants. Haplotype genealogy and analysis of molecular variance
revealed two matrilinear clades (α
h, β
h). Microsatellite analyses of individuals grouped according to their haplotype clade (corresponding group of nuclear genotypes
called α
nuc and β
nuc) revealed significant genotypic differentiation between α
nuc and β
nuc. Such genealogically differentiated forms in a morphologically uniform species are considered indicative of cryptic speciation.
The differentiation was caused by bulls, whereas considering cows only resulted in no differentiation. Such result is best
explained by Haldane’s rule whereby hybrid formation between genealogical forms causes lower viability and fertility of heterogametic hybrids. Although
the lack of hybrid-specific morphological characteristics renders direct testing of reduced hybrid fitness under natural conditions
unfeasible, the effects of Haldane’s rule are demonstrated by reduced male-mediated gene flow between genealogical forms under
sympatric conditions, as was indeed suggested by the data found in Asian elephants: male-mediated gene flow between groups
α
nuc and β
nuc was much lower than female-mediated gene flow.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
相似文献
Joerns FickelEmail: |
1000.
Homology modeling and examination of the effect of the D92E mutation on the H5N1 nonstructural protein NS1 effector domain 总被引:1,自引:0,他引:1
Virulent H5N1 strains of influenza virus often harbor a D92E point mutation in the nonstructural protein NS1. This crucial
mutation has been correlated with increased virulence and/or cytokine resistance, but the structural implications of such
a change are still unclear. Furthermore, NS1 protein could also be a potential target for the development of novel antiviral
agents against H5N1 strains. Therefore, a reasonable 3D model of H5N1 NS1 is important for the understanding of the molecular
basis of increased virulence and the design of novel antiviral agents. Based on the crystal structure of a non-H5N1 NS1 protein,
a model of H5N1 NS1 was developed by homology modeling, molecular mechanics and molecular dynamics simulations. It was found
that the D92E mutation could result in weakened interactions of the carboxylate side chain with other phosphorylated residues,
thereby activating phosphorylation of NS1.
Figure Superposition of snapshots picked from the two molecular dynamic (MD) trajectories: a H5N1 NS1 homology model and b non-H5N1 NS1 crystal structure after 0 (green ribbon), 5 (blue ribbon) and 10 ns (pink ribbon) MD simulation 相似文献