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1.
We report here that Tyrophagus similis and Tyrophagus putrescentiae (Astigmata: Acaridae) have the ability to biosynthesize linoleic acid [(9Z, 12Z)-9, 12-octadecadienoic acid] via a Δ12-desaturation step, although animals in general and vertebrates in particular appear to lack this ability. When the mites were fed on dried yeast enriched with d31-hexadecanoic acid (16:0), d27-octadecadienoic acid (18:2), produced from d31-hexadecanoic acid through elongation and desaturation reactions, was identified as a major fatty acid component of phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs) in the mites. The double bond position of d27-octadecadienoic acid (18:2) of PCs and PEs was determined to be 9 and 12, respectively by dimethyldisulfide (DMDS) derivatization. Furthermore, the GC/MS retention time of methyl 9, 12-octadecadienoate obtained from mite extracts agreed well with those of authentic linoleic acid methyl ester. It is still unclear whether the mites themselves or symbiotic microorganisms are responsible for inserting a double bond into the Δ12 position of octadecanoic acid. However, we present here the unique metabolism of fatty acids in the mites.  相似文献   
2.
Guo W  Lampoudi S  Shea JE 《Proteins》2004,55(2):395-406
The temperature dependence of the free energy landscape of the src-SH3 protein domain is investigated through fully atomic simulations in explicit solvent. Simulations are performed above and below the folding transition temperature, enabling an analysis of both protein folding and unfolding. The transition state for folding and unfolding, identified from the free energy surfaces, is found to be very similar, with structure in the central hydrophobic sheet and little structure throughout the rest of the protein. This is a result of a polarized folding (unfolding) mechanism involving early formation (late loss) of the central hydrophobic sheet at the transition state. Unfolding simulations map qualitatively well onto low-temperature free energy surfaces but appear, however, to miss important features observed in folding simulations. In particular, details of the folding mechanism involving the opening and closing of the hydrophobic core are not captured by unfolding simulations performed under strongly denaturing conditions. In addition, free energy surfaces at high temperatures do not display a desolvation barrier found at lower temperatures, involving the expulsion of water molecules from the hydrophobic core.  相似文献   
3.
What energetic and solvation effects underlie the remarkable two-state thermodynamics and folding/unfolding kinetics of small single-domain proteins? To address this question, we investigate the folding and unfolding of a hierarchy of continuum Langevin dynamics models of chymotrypsin inhibitor 2. We find that residue-based additive Gō-like contact energies, although native-centric, are by themselves insufficient for protein-like calorimetric two-state cooperativity. Further native biases by local conformational preferences are necessary for protein-like thermodynamics. Kinetically, however, even models with both contact and local native-centric energies do not produce simple two-state chevron plots. Thus a model protein's thermodynamic cooperativity is not sufficient for simple two-state kinetics. The models tested appear to have increasing internal friction with increasing native stability, leading to chevron rollovers that typify kinetics that are commonly referred to as non-two-state. The free energy profiles of these models are found to be sensitive to the choice of native contacts and the presumed spatial ranges of the contact interactions. Motivated by explicit-water considerations, we explore recent treatments of solvent granularity that incorporate desolvation free energy barriers into effective implicit-solvent intraprotein interactions. This additional feature reduces both folding and unfolding rates vis-à-vis that of the corresponding models without desolvation barriers, but the kinetics remain non-two-state. Taken together, our observations suggest that interaction mechanisms more intricate than simple Gō-like constructs and pairwise additive solvation-like contributions are needed to rationalize some of the most basic generic protein properties. Therefore, as experimental constraints on protein chain models, requiring a consistent account of protein-like thermodynamic and kinetic cooperativity can be more stringent and productive for some applications than simply requiring a model heteropolymer to fold to a target structure.  相似文献   
4.
As molecules approach one another in aqueous solution, desolvation free energy barriers to association are encountered. Experiments suggest these (de)solvation effects contribute to the free energy barriers separating the folded and unfolded states of protein molecules. To explore their influence on the energy landscapes of protein folding reactions, we have incorporated desolvation barriers into a semi-realistic, off-lattice protein model that uses a simplified physico-chemical force-field determined solely by the sequence of amino acids. Monte Carlo sampling techniques were used to study the effects on the thermodynamics and kinetics of folding of a number of systems, diverse in structure and sequence. In each case, desolvation barriers increase the stability of the native conformation and the cooperativity of the major folding/unfolding transition. The folding times of these systems are reduced significantly upon inclusion of desolvation barriers, demonstrating that the particulate nature of the solvent engenders a more defined route to the native fold.  相似文献   
5.
With the perspective of embarking on a human study using a double iron (Fe) stable isotope tracer protocol to assess iron bioavailability, investigations were conducted on Fe isotope ratios in blood samples using a VG Axiom Multi-collector ICP-MS. The factors affecting the precision and accuracy of Fe isotopic ratios, such as spectral- and matrix-induced interferences and Fe recoveries from sample preparation, have been identified and optimized. Major polyatomic interferences (e.g., Ar-O, Ar-OH, and FeH) were significantly reduced by using an Aridus nebulizer and desolvating system. Isobaric metal (e.g., 54Cr+ on 54Fe+ and 58Ni+ on 58Fe+) interferences and Ca-oxides and hydroxides were quantitatively removed during chemical purification of blood samples and selective isolation of Fe by anion-exchange resin, after mineralization of the blood samples by microwave digestion. Quantitative recoveries of Fe from different steps of sample preparation were verified using whole blood reference material. Fe isotopic compositions of the samples were corrected for instrumental mass bias by the standard-sample bracketing method using the certified reference standard IRMM-014. External precisions on the order of 0.008–0.05 (% RSD), 0.007–0.015 (% RSD), and 0.03–0.09 (% RSD) were obtained for 54Fe/56Fe, 57Fe/56Fe, and 58Fe/56Fe, respectively, in the blood for three replicate measurements. The level of precision obtained in this work enables the detection of low enrichments of Fe in blood, which is highly desired in nutrition tracer studies.  相似文献   
6.
The effects of urea on protein stability have been studied using a model system in which we have determined the energetics of dissolution of a homologous series of cyclic dipeptides into aqueous urea solutions of varying concentration at 25°C using calorimetry. The data support a model in which urea denatures proteins by decreasing the hydrophobic effect and by directly binding to the amide units via hydrogen bonds. The data indicate also that the enthalpy of amide hydrogen bond formation in water is considerably higher than previously estimated. Previous estimates included the contribution of hydrophobic transfer of the α-carbon resulting in an overestimate of the binding between urea and the amide unit of the backbone and an underestimate of the binding enthalpy. Proteins 31:107–115, 1998. © 1998 Wiley-Liss, Inc.  相似文献   
7.
Recent experiments have presented evidence that Watson–Crick hydrogen bonds in a base pair are not absolute requirements for efficient synthesis of that pair by DNA polymerase enzymes. Here we examine quantitative steady-state kinetic data from several published studies involving poorly hydrogen-bonding DNA base analogues and adducts, and analyze the results in terms of solvation, hydrogen bonding, and steric effects. We propose a mechanism that can explain the surprising lack of hydrogen-bonding requirement accompanied by significant selectivity in pairing. This hypothesis makes use of steric matching, enforced both by the tightly confined polymerase active site and by the DNA backbone, as a chief factor determining nucleotide selection during DNA synthesis. The results also suggest that hydrogen bonds from bases to water (solvation) may be important in increasing the effective size of DNA bases, which may help prevent misinsertion of small bases opposite each other. © 1998 John Wiley & Sons, Inc. Biopoly 48: 3–17, 1998  相似文献   
8.
紫杉醇(Paclitaxel,商品名Taxol)是一种在红豆杉科(Taxaceae L.)红豆杉属(Taxus L.)生长缓慢的常绿乔木中分离提取的天然化合物。卡铂和紫杉醇均是目前临床上使用率很高的抗肿瘤药物,并在临床上经常配伍使用治疗不同的癌症。本研究以叶酸偶联的牛血清白蛋白作为药物载体,采用去溶剂技术制备了叶酸靶向卡铂—紫杉醇的白蛋白纳米粒,并研究了靶向制剂体外释放性质。研究结果表明:卡铂—紫杉醇白蛋白纳米粒平均粒径为199.4 nm,Zeta电位为-30.90 mV。卡铂包封率为91.4%;紫杉醇包封率为56.1%,药物总载药量为21%。其冻干粉复溶12 h后各项数据未发生较大变化,说明其具有良好的稳定性。体外释放结果表明叶酸—卡铂—紫杉醇白蛋白纳米粒与卡铂和紫杉醇原粉比较具有明显的缓释效果,体外释药时间可达120 h。  相似文献   
9.
LDL cholesterol (LDL‐C) is cleared from plasma via cellular uptake and internalization processes that are largely mediated by the low‐density lipoprotein cholesterol receptor (LDL‐R). LDL‐R is targeted for lysosomal degradation by association with proprotein convertase subtilisin‐kexin type 9 (PCSK9). Gain of function mutations in PCSK9 can result in excessive loss of receptors and dyslipidemia. On the other hand, receptor‐sparing phenomena, including loss‐of‐function mutations or inhibition of PCSK9, can lead to enhanced clearance of plasma lipids. We hypothesize that desolvation and resolvation processes, in many cases, constitute rate‐determining steps for protein–ligand association and dissociation, respectively. To test this hypothesis, we analyzed and compared the predicted desolvation properties of wild‐type versus gain‐of‐function mutant Asp374Tyr PCSK9 using WaterMap, a new in silico method for predicting the preferred locations and thermodynamic properties of water solvating proteins (“hydration sites”). We compared these results with binding kinetics data for PCSK9, full‐length LDL‐R ectodomain, and isolated EGF‐A repeat. We propose that the fast kon and entropically driven thermodynamics observed for PCSK9‐EGF‐A binding stem from the functional replacement of water occupying stable PCSK9 hydration sites (i.e., exchange of PCSK9 H‐bonds from water to polar EGF‐A groups). We further propose that the relatively fast koff observed for EGF‐A unbinding stems from the limited displacement of solvent occupying unstable hydration sites. Conversely, the slower koff observed for EGF‐A and LDL‐R unbinding from Asp374Tyr PCSK9 stems from the destabilizing effects of this mutation on PCSK9 hydration sites, with a concomitant increase in the persistence of the bound complex. Proteins 2010. © 2010 Wiley‐Liss, Inc.  相似文献   
10.
A practical method to estimate binding free energy, ΔGbind, of a given ligand structure to the target receptor has been developed. The method assumes that ΔGbind is given by the summation of intermolecular interaction energy, ΔGinter, and partial desolvation energy, ΔGdesolv. ΔGdesolv is calculated from the buried surface area in the complex between the ligand and receptor, based on solvation energy, ΔGsolv, formulated by an equation which can be calibrated with observed values. Then, the method was applied to arabinose-binding protein (ABP) and dihydrofolate reductase (DHFR), after recalibrating the weights for ΔGinter and each term of ΔGdesolv using observed ΔGbind data for 29 known ligands to avidin (AV). The usefulness of our method was confirmed by the fact that correlation coefficients between the calculated and observed ΔGbind's in AV, ABP and DHFR were 0.92, 0.77, and 0.88, whereas the corresponding values obtained by simple force field calculation were 0.79, 0.30, and 0.79, respectively. Further investigations to improve the method and validate the parameters are in progress. Proteins 33:62–73, 1998. © 1998 Wiley-Liss, Inc.  相似文献   
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