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41.
Francesca Spyrakis Fátima Lucas Axel Bidon-Chanal Cristiano Viappiani Victor Guallar F. Javier Luque 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(9):1957-1967
This study reports a comparative analysis of the topological properties of inner cavities and the intrinsic dynamics of non-symbiotic hemoglobins AHb1 and AHb2 from Arabidopsis thaliana. The two proteins belong to the 3/3 globin fold and have a sequence identity of about 60%. However, it is widely assumed that they have distinct physiological roles. In order to investigate the structure–function relationships in these proteins, we have examined the bis-histidyl and ligand-bound hexacoordinated states by atomistic simulations using in silico structural models. The results allow us to identify two main pathways to the distal cavity in the bis-histidyl hexacoordinated proteins. Nevertheless, a larger accessibility to small gaseous molecules is found in AHb2. This effect can be attributed to three factors: the mutation Leu35(AHb1) → Phe32(AHb2), the enhanced flexibility of helix B, and the more favorable energetic profile for ligand migration to the distal cavity. The net effect of these factors would be to facilitate the access of ligands, thus compensating the preference for the fully hexacoordination of AHb2, in contrast to the equilibrium between hexa- and pentacoordinated species in AHb1. On the other hand, binding of the exogenous ligand introduces distinct structural changes in the two proteins. A well-defined tunnel is formed in AHb1, which might be relevant to accomplish the proposed NO detoxification reaction. In contrast, no similar tunnel is found in AHb2, which can be ascribed to the reduced flexibility of helix E imposed by the larger number of salt bridges compared to AHb1. This feature would thus support the storage and transport functions proposed for AHb2. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins. 相似文献
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The distribution of residues in a polypeptide sequence is a determinant of aggregation optimized by evolution 下载免费PDF全文
Monsellier E Ramazzotti M de Laureto PP Tartaglia GG Taddei N Fontana A Vendruscolo M Chiti F 《Biophysical journal》2007,93(12):4382-4391
It has been shown that the propensity of a protein to form amyloid-like fibrils can be predicted with high accuracy from the knowledge of its amino acid sequence. It has also been suggested, however, that some regions of the sequences are more important than others in determining the aggregation process. Here, we have addressed this issue by constructing a set of “sequence scrambled” variants of the first 29 residues of horse heart apomyoglobin (apoMb1-29), in which the sequence was modified while maintaining the same amino acid composition. The clustering of the most amyloidogenic residues in one region of the sequence was found to cause a marked increase of the elongation rate (kagg) and a remarkable shortening of the lag phase (tlag) of the fibril growth, as determined by far-UV circular dichroism and thioflavin T fluorescence. We also show that taking explicitly into consideration the presence of aggregation-promoting regions in the predictive methods results in a quantitative agreement between the theoretical and observed kagg and tlag values of the apoMb1-29 variants. These results, together with a comparison between homologous segments from the family of globins, indicate the existence of a negative selection against the clustering of highly amyloidogenic residues in one or few regions of polypeptide sequences. 相似文献
45.
Stephanie Thoms Klaas E.A. Max Michael Wunderlich Tomas Jacso Bernd Reif Franz X. Schmid 《Journal of molecular biology》2009,391(5):918-2651
In previous work, a strongly stabilized variant of the β1 domain of streptococcal protein G (Gβ1) was obtained by an in vitro selection method. This variant, termed Gβ1-M2, contains the four substitutions E15V, T16L, T18I, and N37L. Here we elucidated the molecular basis of the observed strong stabilizations. The contributions of these four residues were analyzed individually and in various combinations, additional selections with focused Gβ1 gene libraries were performed, and the crystal structure of Gβ1-M2 was determined. All single substitutions (E15V, T16L, T18I, and N37L) stabilize wild-type Gβ1 by contributions of between 1.6 and 6.0 kJ mol− 1 (at 70 °C). Hydrophobic residues at positions 16 and 37 provide the major contribution to stabilization by enlarging the hydrophobic core of Gβ1. They also increase the tendency to form dimers, as shown by dependence on the concentration of apparent molecular mass in analytical ultracentrifugation, by concentration-dependent stability, and by a strongly increased van't Hoff enthalpy of unfolding. The 0.88-Å crystal structure of Gβ1-M2 and NMR measurements in solution provide the explanation for the observed dimer formation. It involves a head-to-head arrangement of two Gβ1-M2 molecules via six intermolecular hydrogen bonds between the two β strands 2 and 2′ and an adjacent self-complementary hydrophobic surface area, which is created by the T16L and N37L substitutions and a large 120° rotation of the Tyr33 side chain. This removal of hydrophilic groups and the malleability of the created hydrophobic surface provide the basis for the dimer formation of stabilized Gβ1 variants. 相似文献
46.
The voltammetric assay of Helicobacter pylori DNA was investigated using a bismuth-immobilized carbon nanotube electrode (BCNE). The analytical cyclic voltammetry (CV) peak potential was obtained at a 0.4 V reduction scan, where the diagnostic optimum square-wave (SW) stripping working range was achieved at 0.72-7.92 μg/mL H. pylori DNA (11 points). A relative standard deviation of 1.68% (RSD, n = 5) was obtained with 3.2 mg/mL H. pylori DNA using a 240 s accumulation time. Under optimum conditions, detection limit was 0.06 μg/mL. The developed sensors can be used for clinical application in the 15th doubted human gastric tissues, since the patient's peak current increased a hundred times more than the negative healthy tissue did. The sensing time obtained was only two minutes, and the process was simpler compared to common PCR amplification and electrophoresis photometric detection systems. 相似文献
47.
Yves‐Marie Coïc Charlotte Le Lan Jean‐Michel Neumann Nadège Jamin Françoise Baleux 《Journal of peptide science》2010,16(2):98-104
This work contributes to highlight the benefits of pseudoproline dipeptides introduction in difficult SPPS. We show how a slight modification in the positioning choice conditioned the synthesis achievement of a 54 amino acid long caveolin‐1 peptide encompassing the intramembrane domain. Furthermore, we report a side reaction correlated with the coupling steps and generating truncated fragments with a mass deviation of + 42 Da. Considering the need of structural data for membrane proteins, most of which are considered as prevalent therapeutic targets, chemical synthesis provides an interesting alternative pathway to obtain hydrophobic domains by pushing back the frontiers of conventional RP methods of purification. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
48.
种群分布格局测定的样方尺度效应 总被引:3,自引:0,他引:3
以粤西黑石顶自然保护区西部船底窝的永久样地为研究对象,在一个面积为1600m2的人工次生裸地样地上,借助地理信息系统(GIS)技术,对各个种群分别用3种不同的样方面积(10m×10m,8m×8m,5m×5m)和不同的测定方法来研究演替初期优势种群的分布格局,从而研究不同的样方面积对测定南亚热带森林群落内种群分布格局的影响。结果表明,在南亚热带森林群落演替初期以8m×8m的样方面积来测定种群分布格局较为有效。同时运用GIS技术作数据处理及图形输出,大大简化了分析过程,提高了分析水平。 相似文献
49.
A pair of stereoisomeric covalent adducts to guanine in double-stranded DNA, derived from the reaction of mutagenic and tumorigenic metabolites of benzo[a]pyrene, have been well characterized structurally and thermodynamically. Both high-resolution NMR solution structures and an array of thermodynamic data are available for these 10S (+)- and 10R (-)-trans-anti -[BP]-N(2)-dG adducts in double-stranded deoxyoligonucleotides. The availability of experimentally well-characterized duplexes containing these two stereoisomeric guanine adducts provides an opportunity for evaluating the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method for computing thermodynamic properties from molecular dynamics ensembles. We have carried out 3-ns molecular dynamics simulations, using NMR solution structures as the starting models for the 10S (+)- and 10R (-)-trans-anti-dG adducts in a DNA duplex 11-mer using AMBER 6.0. We employed the MM-PBSA method to compute the free energies, enthalpies, and entropies of the two adducts. Our complete thermodynamic analysis agrees quite well with the full experimental thermodynamic characterization of these adducts, showing essentially equal stabilities of the two adducts. We also calculated the nuclear Overhauser effect (NOE) distances from the molecular dynamics trajectories, and compared them against the experimental NMR-derived NOE distances. Our results showed that the simulated structures are in good agreement with the NMR experimental NOE data. Furthermore, the molecular dynamics simulations provided new structural and biological insights. Specifically, the puzzling observation that the BP aromatic ring system in the 10S (+)-trans-anti-dG adduct is more exposed to the aqueous solvent than the 10R (-)-trans-anti-dG adduct, is rationalized in terms of the adduct structures. The structural and thermodynamic features of these stereoisomeric adducts are also discussed in relation to their reported low susceptibilities to nucleotide excision repair. 相似文献
50.
Giorgia Valle Simona Boncompagni Roberta Sacchetto Feliciano Protasi Pompeo Volpe 《Experimental cell research》2014
Cardiac calsequestrin (CASQ2) contributes to intracellular Ca2+ homeostasis by virtue of its low-affinity/high-capacity Ca2+ binding properties, maintains sarcoplasmic reticulum (SR) architecture and regulates excitation–contraction coupling, especially or exclusively upon β-adrenergic stimulation. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease associated with cardiac arrest in children or young adults. Recessive CPVT variants are due to mutations in the CASQ2 gene. Molecular and ultra-structural properties were studied in hearts of CASQ2R33Q/R33Q and of CASQ2−/− mice from post-natal day 2 to week 8. The drastic reduction of CASQ2-R33Q is an early developmental event and is accompanied by down-regulation of triadin and junctin, and morphological changes of jSR and of SR-transverse-tubule junctions. Although endoplasmic reticulum stress is activated, no signs of either apoptosis or autophagy are detected. The other model of recessive CPVT, the CASQ2−/− mouse, does not display the same adaptive pattern. Expression of CASQ2-R33Q influences molecular and ultra-structural heart development; post-natal, adaptive changes appear capable of ensuring until adulthood a new pathophysiological equilibrium. 相似文献