共查询到20条相似文献,搜索用时 34 毫秒
1.
Omkar Patil 《Molecular simulation》2014,40(14):1147-1156
Folates (and other chromonics molecules) have been shown to self-assemble into ordered structures even at low concentrations. In this study, simulations are used to first replicate the self-assembly of folates and understand why folic acid does not assemble while folate ions do. Subsequently, these simulations replicate the change in structure and behaviour of the assembly with increasing concentration of folates, comparing them to experimental observations in earlier studies. The study then uses fictitious molecules and ions to understand which components of the folate ions drive, or otherwise affect, assembly of the folates and to abstract some guiding principles about structure of chromonics molecules and the impact on assembly. This study shows that while the aromatic rings drive stacking, the hydrophilic groups help solvate and hence control the order of the aromatic stacks, and the 1-ring-diacid moiety controls the orientation of the ions in their plane. 相似文献
2.
Marziyeh Poshteh Shirani Taghi Khayamian Mohammad Dinari Kazem Karami Zohreh Mehri-Lighvan 《Journal of biomolecular structure & dynamics》2013,31(16):4156-4169
New folic acid-conjugated mesoporous silica nanoparticles were synthesized. The effect of calcination at 400°C on the fluorescence characteristics of mesoporous silica nanoparticles were studied in this work. The formed carbon dots (CDs) from calcination were used as the source of fluorescence. 3-Aminopropyltriethoxysilane was then used to amine-functionalized the fluorescent surface of mesoporous silica nanoparticles. The amine fluorescence mesoporous silica nanoparticles (amine-FMSNs) were coupled with folic acid (FA) as the target ligand (FA-amine-FMSNs). A palladium complex was also synthesized and encapsulated in the FA-amine-FMSNs yielded fluorescent property with therapeutic effect. The in vitro release of an entrapped palladium complex from FA-amine-FMSNs was studied under physiological conditions. According to the cell viability assay on HeLa (positive FR) and Hep-G2 (negative FR) cells, the targeted delivery system inhibited the growth of positive FR with higher selectivity compared with negative FR cells. Also, the emission CDs were used for fluorescence microscopic imaging. To confirm anti-cancer activity of the palladium complex, the interaction between palladium complex and G-quadruplex DNA were investigated with multi-spectroscopic methods and molecular modeling. The molecular docking studies showed a partial intercalation mode with a 4.27 × 105 M?1 binding constant. 相似文献
3.
Abhi Das 《Journal of biomolecular structure & dynamics》2016,34(4):800-813
The interaction of the plant alkaloid aristololactam-β-D-glucoside (ADG) and the anticancer agent daunomycin (DAN) with human hemoglobin was studied by different spectroscopic and calorimetric methods. The binding affinity values of ADG and DAN, estimated from spectroscopic experiments, were 3.79 × 104 and 6.68 × 104 M?1, respectively. From circular dichroism, 3D fluorescence, and FTIR studies it was observed that, DAN induced stronger conformational changes than ADG in the protein. From synchronous fluorescence spectroscopy results, a pronounced shift in the maximum emission wavelength of tyrosine residues was observed in both cases suggesting that the drugs changed the polarity around tyrosine residues with marginal change around the tryptophan residues. The thermodynamics of the binding interaction analyzed using microcalorimetry presented single binding events that were exothermic in nature in both cases. The binding was driven by large positive standard molar entropy changes with small favorable enthalpy contributions. Negative heat capacity changes in both cases are correlated to the involvement of significant hydrophobic forces in the complexation process. The affinity of DAN to Hb was higher than that of ADG. 相似文献
4.
Urszula Śliwińska-Hill Katarzyna Wiglusz 《Journal of biomolecular structure & dynamics》2013,31(14):3731-3739
AbstractThe interaction between glycated human serum albumin (gHSA) and folic acid (FA) was investigated by various spectroscopic techniques, such as fluorescence, circular dichroism, UV–vis absorption spectroscopy and electrophoretic light scattering technique. These methods characterize the binding properties of an albumin–folic acid system. The binding constants values (Ka) at 300 and 310 K are about 104 M?1. The standard enthalpy change (ΔH) and the standard entropy change (ΔS) were calculated to be ~?20?kJ mol?1 and ~16 J mol?1 K?1, respectively, which indicate characteristic electrostatic interactions between gHSA and folic acid. The CD studies showed that there are no significant conformational changes in the secondary structure of the protein. Moreover, the zeta potential measurements proved that under physiological conditions the gHSA–folic acid complex shows instability. No significant changes in the secondary structure of the protein and reversible drug binding are the desirable effect from pharmacological point of view.Communicated by Ramaswamy H. Sarma 相似文献
5.
Sameer Shakeel Ansari Rizwan Hasan Khan 《Journal of biomolecular structure & dynamics》2013,31(13):3362-3375
Intermolecular interaction study of human serum albumin (HSA) with two anthraquinones i.e. danthron and quinizarin has been performed through fluorescence, UV-vis and CD spectroscopy along with docking analysis. The titration of drugs into HSA solution brought about the quenching of fluorescence emission by way of complex formation. The binding constants were found to be 1.51 × 104 L mol?1 and 1.70 × 104 L mol?1 at λexc = 280 nm while at λexc = 295 nm, the values of binding constants were 1.81 × 104 L mol?1 and 1.90 × 104 L mol?1 which hinted toward binding of both the drugs in the vicinity of subdomain IIA. Different temperature study revealed the presence of static quenching mechanism. Moreover, more effective quenching of the fluorescence emission was observed at λexc = 295 nm which also suggested that both the drug molecule bind nearer to Trp-214. Thermodynamic parameters showed that hydrophobic interaction was the major force behind the binding of drugs. The UV-vis spectroscopy testified the formation of complex in both the systems and primary quenching mechanism as static one. The changes in secondary structure and α-helicity in both the systems were observed by circular dichroism spectroscopy. Furthermore, molecular docking analysis predicted the probable binding site of drugs in subdomain IIA of HSA molecule. The types of amino acid residues surrounding the drug molecule advocated that van der Waals forces, hydrophobic forces and electrostatic forces played a vital role in the stabilization of drug-protein complex formed. 相似文献
6.
Somaye Shahraki Ali Heydari Maryam Saeidifar Masoumeh Gomroki 《Journal of biomolecular structure & dynamics》2013,31(14):3651-3665
Small globular protein, β-lactoglobulin (βLG), which has significant affinity toward many drugs, is the most abundant whey protein in milk. In this study, the interaction of βLG with three important nutrients, ascorbic acid (ASC), folic acid (FOL), and vitamin K3 (VK3) was investigated by spectroscopic methods (UV–visible and fluorescence) along with molecular docking technique. The results of fluorescence measurements showed that studied nutrients strongly quenched βLG fluorescence in static (FOL and ACS) or static–dynamic combined quenching (VK3) mode. The values of binding constants (KβLG-ASC ~ 4.34 × 104 M?1, KβLG-FOL ~ 1.67 × 104 M?1and KβLG-VK3 ~ 13.49 × 104 M?1 at 310 K) suggested that VK3 and FOL had stronger binding affinity toward βLG than ASC. Thermodynamic analysis indicated that hydrophobic interactions are the major forces in the stability of FOL–βLG complex with enthalpy- and entropy-driving mode while, hydrogen bonds and van der Waals interactions play a major role for βLG–ASC and βLG–VK3 associations. The results of 3D fluorescence FT-IR and UV–Visible measurements indicated that the binding of above nutrients to βLG may induce conformational and micro-environmental changes of protein. Also, there is a reciprocal complement between spectroscopic techniques and molecular docking modeling. The docking results indicate that the ASC, FOL, and VK3 bind to residues located in the subdomain B of βLG. Finally, this report suggests that βLG could be used as an effective carrier of above nutrients in functional foods. 相似文献
7.
Chabita Saha Rahul Kumar Asmita Das 《Journal of biomolecular structure & dynamics》2017,35(12):2531-2538
Histones are associated with DNA to form nucleosome essential for chromatin structure and major nuclear processes like gene regulation and expression. Histones consist of H1, H2A, H2B and H3, H4 type proteins. In the present study, combined histones from calf thymus were complexed with ct DNA and their binding affinities were measured fluorimetrically. All the five histones were resolved on SDS page and their binding with DNA was visualized. The values of biding affinities varied with pH and salt concentration. Highest affinity (4.0?×?105 M?1) was recorded at pH 6.5 in 50 mM phosphate buffer and 1.5?×?104 M?1 in 2 M NaCl at pH 7.0. The CD spectra support the highest binding affinity with maximum conformational changes at pH 7.0. The time-resolved fluorescence data recorded two life times for histone tyrosine residues at 300 nm emission in phosphate buffer pH 6.5. These life times did not show much change upon binding with DNA in buffer as well as in 2 M NaCl. The isothermal calorimetric studies yielded thermodynamic parameters ΔG, ΔH and ΔS as ?1.6?×?105 cal/mol, ?1.13?×?103 cal/mol and ?3.80 cal/mol/deg, respectively, evidencing a spontaneous exothermic reaction. The dominant binding forces in building the nucleosome are electrostatic interactions. 相似文献
8.
Sabine Rudolph-Bhner Daniela Quarzago Michael Czisch Ulf Ragnarsson Luis Moroder 《Biopolymers》1997,41(6):591-606
Enkephalin represents one of the bioactive peptide molecules most extensively investigated both in solution and in the crystal state. Depending upon the environment chosen for such studies, three main conformational states were identified for this flexible, linear pentapeptide—i.e., an extended conformation, a single-bend, and a double-bend structure. Since CD and Fourier transform ir (FTIR) spectra of Leu-enkephalin solubilized in negatively charged reverse micelles of bis (2-ethylhexyl)sulfosuccinate sodium salt/isooctane/water were supportive of a restricted conformational space of the aromatic side chains and of a bended type fold, we have analyzed by nmr the conformational preferences of Leu-enkephalin in reverse micelles using a synthetic [13C, 15N]-backbone-labeled sample. The overall conformation derived from nuclear Overhauser effect spectroscopy (NOESY) and 15N-filtered rotating frame NOESY (ROESY) spectra and by distance geometry calculations is a double-bend fold of the backbone that is comparable to one of the known x-ray structures. Thereby the tyrosine side chain is inserted into the hydrophobic core of the reverse micelles in a restrained conformational space as well evidenced by NOEs between the aromatic ring protons and the surfactant. The proximity of the aromatic rings of tyrosine and phenylalanine indicate a preferred structure consistent with the postulated conformation of the opioid peptide in the δ-receptor-bound state. These results confirm the interesting and promising properties of reverse micelles as membrane mimetica. © 1997 John Wiley & Sons, Inc. Biopoly 41: 591–606, 1997 相似文献
9.
Peder Olesen Larsen Detlef K. Onderka Heinz G. Floss 《Biochimica et Biophysica Acta (BBA)/General Subjects》1975,381(2):397-408
14C-labelled shikimic acid and double labelled shikimic acid tritiated stereospecifically at C-6 are incorporated into 3-(3-carboxyphenyl)alanine, 3-(3-carboxyl-4-hydroxyphenyl)alanine, phenylalanine, and tyrosine in Resda lutea L., Reseda odoratta L., Iris x Hollandica cv. Prof. Blauw, and Iris x hollandica cv. Wedgwood. The experiments with 14C-labelled shikimic acid confirm that the aromatic carboxyl groups and rings in 3-(3-carboxyphenyl)-alanine and 3-(3-carboxy-4-hydroxyphenyl)alanine derive from the carboxyl group and ring in shikimic acid whereas the experiments with double labelled shikimic acid demonstrate that the pro-6S-hydrogen atom is retained and the pro-6R-hydrogen atom lost in the biosynthesis of 3-(3-carboxyphenyl)alanine, phenylalanine, and tyrosine in the plants used. 3H was located in the ortho-position in the aromatic rings of phenylalanine and tyrosine but in a position para to the alanine side chain of 3-(3-cabroxyphenyl)alanine. No 3H was found in 3-(3-carboxy-4-hydroxyphenyl)alanine. This supports a derivation of the last two compounds from chorismic acidvia isochorismic acid, isoprephenic acid, and 3′-carboxyphenylpyruvic acid and 3′-carboxy-4′-hydroxyphenylpyruvic acid. The 3H/14 C ratio in 3-(3-carboxyphenyl)alanine was found higher than in the precursor used. This isotope effect must operate by competition between the pathways from isoprephenic acid to 3′-carboxyphenylpyruvic acid and to 3′-carboxy-4′-hydroxyphenylpyruvic acid. The proposed biosynthetic pathways for the two carboxy-substituted amino acids are in agreement with their distribution patterns in the plant kingdom and suggest that they may derive from minor changes of enzymes involved in the general pathways of aromatic biosynthesis. 相似文献
10.
Sowrirajan Chandrasekaran Natesan Sudha D. Premnath 《Journal of biomolecular structure & dynamics》2013,31(9):1945-1956
This work deals with the synthesis of 6-methyl-3-[(4′-methylphenyl)imino]methyl-4H-chromen-4-one (MMPIMC), its binding to β-cyclodextrin, and the influence of the cyclodextrin complexation on the compound’s binding to bovine serum albumin (BSA). The 1:2 stoichiometry for the complexation of MMPIMC with β-cyclodextrin is determined with the binding constant of 1.90 × 104 M?2. The structure of host–guest complex plays a role in protein binding of MMPIMC. One- and two-dimensional NMR spectra are used to determine the mode of binding of the guest to β-cyclodextrin cavity and the structure of the inclusion complex is proposed. The binding of MMPIMC with BSA in the absence and the presence of β-cyclodextrin is studied. The binding strengths of MMPIMC–BSA (1.73 × 105 M?1) and β-cyclodextrin-complexed MMPIMC–BSA (9.0 × 104 M?1) show difference in magnitude. The Förster Resonance Energy Transfer efficiency and the proximity of the donor and acceptor molecules, are modulated by β-cyclodextrin. Molecular modeling is used to optimize the sites and mode of binding of MMPIMC with bovine serum albumin. 相似文献
11.
Daniel Pushpa Raju Yeggoni Darla Mark Manidhar Cirandur Suresh Reddy 《Journal of biomolecular structure & dynamics》2016,34(9):2023-2036
Coumarin molecules have biological activities possessing lipid-controlling activity, anti-hepatitis C activity, anti-diabetic, anti-Parkinson activity, and anti-cancer activity. Here, we have presented an inclusive study on the interaction of 8-substituted-7-hydroxy coumarin derivatives (Umb-1/Umb-2) with α-1-glycoprotein (AGP) and human serum albumin (HSA) which are the major carrier proteins in the human blood plasma. Binding constants obtained from fluorescence emission data were found to be KUmb-1=3.1 ± .01 × 104 M?1, KUmb-2 = 7 ± .01 × 104 M?1, which corresponds to ?6.1 and ?6.5 kcal/mol of free energy for Umb-1 and Umb-2, respectively, suggesting that these derivatives bind strongly to HSA. Also these molecules bind to AGP with binding constants of KUmb-1-AGP=3.1 ± .01 × 103 M?1 and KUmb-2-AGP = 4.6 ± .01 × 103 M?1. Further, the distance, r between the donor (HSA) and acceptor (Umb-1/Umb-2) was calculated based on the Forster’s theory of non-radiation energy transfer and the values were observed to be 1.14 and 1.29 nm in Umb-1–HSA and Umb-2–HSA system, respectively. The protein secondary structure of HSA was partially unfolded upon binding of Umb-1 and Umb-2. Furthermore, site displacement experiments with lidocaine, phenylbutazone (IIA), and ibuprofen (IIIA) proves that Umb derivatives significantly bind to subdomain IIIA of HSA which is further supported by docking studies. Furthermore, Umb-1 binds to LYS402 with one hydrogen bond distance of 2.8 Å and Umb-2 binds to GLU354 with one hydrogen bond at a distance of 2.0 Å. Moreover, these molecules are stabilized by hydrophobic interactions and hydrogen bond between the hydroxyl groups of carbon-3 of coumarin derivatives. 相似文献
12.
Conjugation to folic acid is known to enhance the uptake of molecules by human cells that over-produce folate receptors. Variants of bovine pancreatic ribonuclease (RNase A) that have attenuated affinity for the endogenous ribonuclease inhibitor protein (RI) are toxic to mammalian cells. Here, the random acylation of amino groups in wild-type RNase A with folic acid is shown to decrease its catalytic activity dramatically, presumably because of the alteration to a key active-site residue, Lys41. To effect site-specific coupling, Nδ-bromoacetyl-Nα-pteroyl-l-ornithine, which is a folate analogue with an electrophilic bromoacetamido group, was synthesized and used to S-alkylate Cys88 of the G88C variant of RNase A. The pendant folate moiety does not decrease enzymatic activity, enables RI-evasion, and endows toxicity for cancer cells that over-produce the folate receptor. These data reveal a propitious means for targeting proteins and other molecules to cancer cells. 相似文献
13.
M. Moradi A.A. Saboury B. Ghalandari A.R. Harifi 《Journal of biomolecular structure & dynamics》2013,31(10):2255-2266
Deferasirox (DFX), as an oral chelator, is used for treatment of transfusional iron overload. In this study, we have investigated the effects of DFX as an iron chelator, on the function and structure of bovine liver catalase (BLC) by different spectroscopic methods of UV–visible, fluorescence, and circular dichroism (CD) at two temperatures of 25 and 37 °C. In vitro kinetic studies showed that DFX can inhibit the enzymatic activity in a competitive manner. K I value was calculated 39 nM according to the Lineweaver–Burk plot indicating a high rate of inhibition of the enzyme. Intrinsic fluorescence data showed that increasing the drug concentrations leads to a significant decrease in the intrinsic emission of the enzyme indicating a significant change in the three-dimensional environment around the chromophores of the enzyme structure. By analyzing the fluorescence quenching data, it was found that the BLC has two binding sites for DFX and the values of binding constant at 25 and 37 °C were calculated 1.7 × 107 and 3 × 107 M?1, respectively. The static type of quenching mechanism is involved in the quenching of intrinsic emission of enzyme. The thermodynamic data suggest that hydrophobic interactions play a major role in the binding reaction. UV–vis spectroscopy results represented the changes in tryptophan (Trp) absorption and Soret band spectra, which indicated changes in Trp and heme group position caused by the drug binding. Also, CD data represented that high concentrations of DFX lead to a significant decreasing in the content of β-sheet and random coil accompanied an increasing in α-helical content of the protein. The molecular docking results indicate that docking may be an appropriate method for prediction and confirmation of experimental results and also useful for determining the binding mechanism of proteins and drugs. According to above results, it can be concluded that the DFX can chelate the Fe(III) on the enzyme active site leading to changes in the function and structure of catalase which can be considered as a side effect of this drug and consequently has an important role in hepatic complications and fibrosis. 相似文献
14.
John C. Mathers 《Genes & nutrition》2009,4(3):173-178
Folate is a B vitamin required for one-carbon transfer reactions including methylation of cell macromolecules including DNA and synthesis of the purines adenosine and guanosine and the pyrimidine thymidine. Epidemiological evidence suggests that diets providing higher amounts of folates lower the risk of colo-rectal cancer (CRC) and these observations are supported by plausible biological mechanisms. Inadequate folate supply results in DNA damage through (a) the incorporation of uracil (in place of thymidine) into DNA and subsequent unsuccessful attempts at DNA repair and (b) aberrant patterns of DNA methylation. However, human intervention studies using relatively large doses (500–5,000 μg/day) of folic acid (a synthetic form of folate) have provided no evidence of benefit in terms of adenoma recurrence. Indeed, there is some evidence of potential harm in increased risk of prostate cancer. Possible reasons for the apparent divergence in findings from the observational and intervention studies include the use of (unphysiologically) large doses of folic acid in the intervention studies whereas smaller intakes of food folates appeared to offer “protection” against CRC in case–control and prospective cohort studies. With intakes of folic acid greater than 400 μg/day, unmetabolised folic acid appears in peripheral blood and there are suggestions that this folic acid may have adverse effects e.g. reduced cytotoxicity of Natural Killer cells. Until the benefit-risk relationship associated with mandatory fortification with folic acid has been clarified (and, in particular, the possible risk of inducing extra cases of bowel or other cancer), it would seem wise to delay further mandatory folic acid fortification. 相似文献
15.
Uptake of folic acid was measured in secondary cultures of skin fibroblasts from fetal rats. The cultures were made quiescent by 24 hours preincubation in medium containing 1% serum and subsequent 3 hours preincubation in phosphate buffered saline. The uptake of 3H-folic acid was linear with time during 15 seconds and reached a plateau level at 2–3 minutes. There was no further increase in the intracellular radioactivity until the end of the experiments at 10 minutes. The uptake of folic acid in fibroblasts was not concentrative and proceeded until equilibration with the extracellular concentration. Intracellular metabolic conversion of folic acid was not significant during the time of the experiments (up to 10 minutes). Insulin caused a two-fold increase in the initial rate of folate uptake as determined from the 15 second uptake values. The dose response curves for the insulin effect showed that 85% of the maximal effect was exerted by 1 m?M insulin. A lag period of 7–10 minutes was observed after the addition of insulin and before the effect on folic acid uptake was manifested. Thereafter the effect increased with the time of preincubation with insulin. The concentration dependence of folate uptake yielded non homogeneous curves. At low concentrations of substrate, saturable components were observed while at high concentration (above 5 × 10?6 M) a linear component was observed. Insulin increased the slope of the linear component and the Vmax of the saturable component while the Km remained unaltered. 相似文献
16.
Marcelo Aguiar Costa-Lima Márcia Rodrigues Amorim Iêda Maria Orioli 《Molecular biology reports》2013,40(3):2115-2125
The association between Down syndrome (DS) and maternal polymorphisms in genes encoding folic acid metabolizing enzymes remains a controversial issue. A meta-analysis was performed to evaluate the association of maternal MTHFR 677C > T polymorphism and the risk of having a child with DS. Case–control studies were screened from major literature databases. Twenty articles from 13 countries worldwide, with a total of 2,101 DS and 2,702 control mothers, attended the inclusion criteria. We found a 50 % increase for the association of maternal homozygous TT genotype and DS in both fixed (OR = 1.51; 95 % CI 1.22–1.87) and random effects models (OR 1.54; 95 % 1.15–2.05). Similarly, a significant pooled OR was found for the heterozygote CT, with an OR 1.26; 95 % CI 1.10–1.43 (fixed effects model) and OR 1.28; 95 % 1.08–1.51 (random effects model). As ultra-violet B solar radiation highly depends on latitude, and can promote, in less pigmented skin, intravascular folate photolysis, we stratified the analysis by latitude region, defining as Tropical (between 23.5° S and 23.5° N), Sub-Tropical (between 23.5° and 40° N and S), and Northern (≥40o N). Significant association was only found for Sub-Tropical area, both using fixed and random effect models. In conclusion, MTHFR 677C > T polymorphism is a moderate risk factor for DS for some populations, and populations located in Sub-Tropical region seem to be at greater risk. Latitude, ethnicity, skin pigmentation, and red blood cell folate are important variables to be considered in future studies. 相似文献
17.
Maternal smoking during pregnancy may affect newborn DNA methylation (DNAm). However, little is known about how these associations vary by a newborn’s sex and/or maternal nutrition. To fill in this research gap, we investigated epigenome-wide DNAm associations with maternal smoking during pregnancy in African American mother-newborn pairs. DNAm profiling in cord (n = 379) and maternal blood (n = 300) were performed using the Illumina HumanMethylation450 BeadChip array. We identified 12 CpG sites whose DNAm levels in cord blood were associated with maternal smoking, at a false discovery rate <5%. The identified associations in the GFI1 gene were more pronounced in male newborns than in females (P = 0.002 for maternal smoking × sex interaction at cg18146737). We further observed that maternal smoking and folate level may interactively affect cord blood DNAm level at cg05575921 in the AHRR gene (P = 5.0 × 10?4 for interaction): compared to newborns unexposed to maternal smoking and with a high maternal folate level (>19.2 nmol/L), the DNAm level was about 0.03 lower (P = 3.6 × 10?4) in exposed newborns with a high maternal folate level, but was 0.08 lower (P = 1.2 × 10?8) in exposed newborns with a low maternal folate level. Our data suggest that adequate maternal folate levels may partly counteract the impact of maternal smoking on DNAm. These findings may open new avenues of inquiry regarding sex differences in response to environmental insults and novel strategies to mitigate their intergenerational health effects through optimization of maternal nutrition. 相似文献
18.
Ligand binding studies on carrier proteins are crucial in determining the pharmacological properties of drug candidates. Here, a new palladium(II) complex was synthesized and characterized. The in vitro binding studies of this complex with two carrier proteins, human serum albumin (HSA), and β-lactoglobulin (βLG) were investigated by employing biophysical techniques as well as computational modeling. The experimental results showed that the Pd(II) complex interacted with two carrier proteins with moderate binding affinity (Kb ≈ .5 × 104 M?1 for HSA and .2 × 103 M?1 for βLG). Binding of Pd(II) complex to HSA and βLG caused strong fluorescence quenching of both proteins through static quenching mechanism. In two studied systems hydrogen bonds and van der Waals forces were the major stabilizing forces in the drug-protein complex formation. UV–Visible and FT-IR measurements indicated that the binding of above complex to HSA and βLG may induce conformational and micro-environmental changes of two proteins. Protein–ligand docking analysis confirmed that the Pd(II) complex binds to residues located in the subdomain IIA of HSA and site A of βLG. All these experimental and computational results suggest that βLG and HSA might act as carrier protein for Pd(II) complex to deliver it to the target molecules. 相似文献
19.
L T Murthy 《Life sciences》1975,17(12):1777-1783
Inhibitors of phenylalanine hydroxylase and tyrosine hydroxylase were used in the assay of phenylalanine hydroxylase in liver and kidney of rats and mice. Parachlorophenylalanine (PCPA), methyl tyrosine methyl ester and dimethyl tyrosine methyl ester showed 5–15% inhibition while α-methyl tyrosine seemed to inhibit phenylalanine hydroxylase to the extent of 95–98% at concentrations of 5 × 10 −5M –1 × 10 −4M. After a phenylketonuric diet (0.12% PCPA + 3% excess phenylalanine), the liver showed 60% phenylalanine hydroxylase activity and kidney 82% that present in pair-fed normals. Hepatic activity was normal after 8 days refeeding normal diet whereas kidney showed 63% of normal activity. The PCPA-fed animals showed 34% in liver and 38% in kidney as compared to normals; in both cases normal activity was noticed after refeeding. The phenylalanine-fed animals showed activity similar to that seen in phenylketonuric animals. The temporary inducement of phenylketonuria in these animals may be due to a slight change in conformation of the phenylalanine hydroxylase molecule; once the normal diet is resumed, the enzyme reverts back to its active form. This paper also suggests that α-methyl tyrosine when fed in conjunction with the phenylketonuric diet may suppress phenylalanine hydroxylase activity completely in the experimental animals thus yielding normal tyrosine levels as seen in human phenylketonurics. 相似文献
20.
The Archaebacterium Thermoplasma acidophilum has a histone-like protein (HTa) abundantly associated with its deoxyribonucleic acid. Each native tetrameric complex of HTa contains 20 phenylalanine residues, 4 tyrosine residues, and no tryptophan. When the protein was excited by radiation at 252 nm, which is a wavelength absorbed predominantly by phenylalanine, the fluorescent emission was mostly from tyrosine. According to the excitation spectrum for this tyrosine fluorescence, the cause was energy transfer from phenylalanine, which occurred with about 50% efficiency. When the tyrosine residues were removed enzymatically, the excited-state lifetime of the phenylalanine residues nearly doubled. Because of energy transfer, the tyrosine emission had two apparent fluorescence decay lifetimes; one lifetime (3.9 ns) was that of tyrosine while the second (12.1 ns) corresponded to the excited state of phenylalanine. 相似文献