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Hong-Yu Zhang

Publications and source records attributed to Hong-Yu Zhang.

At least 19 recordsLinked to original sources
PubMed2007

Density functional theory methods as powerful tools to elucidate amino acid oxidation mechanisms. A case study on methionine model peptide.

The amino acid oxidation mechanism has been a research focus in recent years. Although various experimental techniques have been employed to address the problem, it is still a great challenge to identify the oxidation intermediates of amino acids. To explore the potential of theoretical methods in helping elucidating amino acid oxidation mechanisms, one-electron oxidation of a methionine model peptide (N-acetylmethionine amide) was investigated by density functional theory (DFT; including TD-DFT) calculations. The theoretical results not only testified the experimentally identified oxidation mechanisms of the peptide to a large extent but also revealed the contribution of protonated species to the peptide oxidation. All of these findings strongly suggest that DFT methodology has great potential in investigating amino acid oxidation mechanisms.

Amides↗
PubMed2007

Protein architecture chronology deduced from structures of amino acid synthases.

Inferring the protein architecture chronology is one of central topics in origin of life study and has been given much attention. Based on an amino acid evolutionary model that late amino acids were bio-synthesized prior to early counterparts, we addressed the issue by examining the structures of amino acid synthases. Despite the limited structural information on amino acid synthases, our deduction revealed that alpha/beta was the oldest protein class, which is in good agreement with the prior fold-usage-based conclusion.

Amino Acid Sequence↗
PubMed2006

Neighboring-site effects of amino acid mutation.

Although the context dependence of nucleotide mutation has been supported by accumulating theoretical and experimental evidence, whether this effect can be extended to amino acid mutation remains obscure. As the amino acid doublets (20 x 20) are much more diverse than their nucleotide counterparts (4 x 4), any attempt to address the neighboring-site effects of amino acid mutation was frustrated by deficient amino acid mutation data. Based on the recently revealed 599,745 mutation sites in 45,137 orthologous proteins, we provide solid evidence for the first time to support the existence of neighboring-site effects in amino acid mutation, which is significantly important to improving the prevalent protein-evolution models.

Amino Acid Sequence↗
PubMed2006

Direct correlation between proteins' folding rates and their amino acid compositions: an ab initio folding rate prediction.

Discovering the mechanism of protein folding, in molecular biology, is a great challenge. A key step to this end is to find factors that correlate with protein folding rates. Over the past few years, many empirical parameters, such as contact order, long-range order, total contact distance, secondary structure contents, have been developed to reflect the correlation between folding rates and protein tertiary or secondary structures. However, the correlation between proteins' folding rates and their amino acid compositions has not been explored. In the present work, we examined systematically the correlation between proteins' folding rates and their amino acid compositions for two-state and multistate folders and found that different amino acids contributed differently to the folding progress. The relation between the amino acids' molecular weight and degeneracy and the folding rates was examined, and the role of hydrophobicity in the protein folding process was also inspected. As a consequence, a new indicator called composition index was derived, which takes no structure factors into account and is merely determined by the amino acid composition of a protein. Such an indicator is found to be highly correlated with the protein's folding rate (r > 0.7). From the results of this work, three points of concluding remarks are evident. (1) Two-state folders and multistate folders have different rate-determining amino acids. (2) The main determining information of a protein's folding rate is largely reflected in its amino acid composition. (3) Composition index may be the best predictor for an ab initio protein folding rate prediction directly from protein sequence from the standpoint of practical application.

Amino Acid Sequence↗
PubMed2006

Same causes, same cures.

Thanks to the continuing bio-medicinal efforts, similar causes underlying the pathogenesis of Alzheimer's disease (AD) and prion diseases (PDs) have been revealed, which include oxidative stress, excessive transition metal ions, and misfolded/aggregated proteins. Therefore, the therapeutic strategy for one disease may be effective for the other. More interestingly, accumulating evidence indicates that not just the strategies but also the prescriptions may be shared by AD and PD treatments. In this review, we first summarize the known dual fighters against AD and PDs (which include antioxidants, metal chelators, and protein aggregation inhibitors), and then indicate that some super-dual-fighters may hit multiple targets implicated in AD and PDs, whose structural features highlight the importance of aromatic moiety and phenolic groups. These findings not only provide important clues to accelerating the screening of anti-AD and anti-PDs drugs but also help to understand the etiology of AD and PDs.

Alzheimer Disease↗
PubMed2006

8-Chloro-adenosine inhibits growth at least partly by interfering with actin polymerization in cultured human lung cancer cells.

A key feature of actin is its ability to bind and hydrolyze ATP. 8-Chloro-adenosine (8-Cl-Ado), which can be phosphorylated to the moiety of 8-Cl-ATP in living cells, inhibits tumor cell proliferation. Therefore we tested the hypothesis that 8-Cl-Ado can interfere with the dynamic state of actin polymerization. We found that 8-Cl-Ado inhibited the growth of human lung cancer cell line A549 and H1299 in culture, and arrested the target cells in G2/M phase evidenced by fluorescence-activated cell sorting (FACS). Immunocytochemistry showed that the normal organization of microfilaments was disrupted in 8-Cl-Ado-exposed cells, which is accompanied by the decrease of cell size and the alteration of cell shape, and by aberrant mitosis and apoptosis in targeted cells. Furthermore, in vitro light scattering assays revealed that 8-Cl-ATP could directly inhibit the transition of G-actin to F-actin. DNase I inhibition assays showed that the G/F-actin ratio, a surrogate marker of actin polymerization status in living cells, was significantly increased in 8-Cl-Ado-exposed A549 and H1299 cells, compared to the G/F-actin ratio in unexposed cells. Taken together, these results indicate that 8-Cl-Ado exposure can alter the dynamic properties of actin polymerization, disrupt the dynamic instability or the rearrangement ability of actin filaments. Therefore, our data suggest that 8-Cl-Ado may exert its cytotoxicity at least partly by interfering with the dynamic instability of microfilaments, which may correlate with its inhibitory effects on cell proliferation and cell death.

2-Chloroadenosine↗
PubMed2006

Proton dissociation is important to understanding structure-activity relationships of gallic acid antioxidants.

Gallic acid derivatives (GADs) can efficiently scavenge free radicals, which is partially responsible for their neuroprotective effects. As GADs tend to deprotonate to give birth to GAD anions, which has big influence on the radical-scavenging behaviors of GADs, to understand the structure-activity relationships (SARs) of GAD antioxidants, the anions should be taken into consideration. In this paper, a combined density functional theory method, labeled as (RO)B3LYP/6-311+G(2d,2p)//AM1/AM1, was employed to calculate homolytic O-H bond dissociation enthalpies and adiabatic ionization potentials for GADs and derived anions in solvent (ethanol), by which the experimentally observed SARs of GADs were better elucidated.

Antioxidants↗
PubMed2006

Di- and tetranuclear metal complexes with phenoxo bridges: synthesis, structures, and photoluminescent and electroluminescent properties.

Dinuclear and tetranuclear copper 2,6-bis(2-hydroxyphenyl)pyridine (H(2)L) complexes Cu2(L)2(py)2 (1) and Cu4(L)4(DMF) (2) were synthesized. The complexes 1 and 2 were characterized by elemental analyses, mass spectrometry, and single-crystal X-ray diffraction analyses. 1 crystallizes in the monoclinic space group P2(1)/n with a = 13.330(2) Angstroms, b = 9.361(1) Angstroms, c = 14.676(1) Angstroms, beta = 100.94(1) degrees, V = 1798.1(3) Angstroms(3), and Z = 2. 2 crystallizes in the monoclinic space group P2(1)/n with a = 13.360(1) Angstroms, b = 14.884(1) Angstroms, c = 15.462(2) Angstroms, beta = 97.50(4) degrees, V = 3048.4(1) Angstroms(3), and Z = 2. Tetranuclear zinc complex Zn4(L)4(py)4 (3) was prepared and characterized by X-ray diffraction. 3 crystallizes in the triclinic space group P with a = 13.770(1) Angstroms, b = 15.465(1) A, c = 16.409(2) Angstroms, alpha = 88.877(9) degrees, beta = 88.035(4) degrees, gamma = 82.956(3) degrees, V = 3465.6(5) Angstroms(3), and Z = 2. The di- and tetranuclear complexes 1-3contain phenoxo bridges. 1 is a dinuclear complex with two Cu(II) centers, two py ligands, and two L ligands, and each L ligand donates its pyridyl ring and one of the phenolate groups to one metal and shares the other phenolate group between both metals, affording a Cu(2)(mu-O)(2) core. 2, in contrast, is a tetranuclear complex with four Cu(II) centers and four L ligands. Two of the L ligands have the same coordination mode as 1, and the other two L ligands donate their pyridyl rings to one metal and share both phenolate groups between four metals, resulting in three four-membered Cu2(mu-O)2 rings, which joined each other and showed great distortion from planarity. 3 is a tetranuclear complex with four Zn(II) centers, four pyridine ligands, and four L ligands, and the L ligands have the same coordination modes as those of 2. Single-crystal X-ray analysis showed that hydrogen-bonding and pi-pi stacking interactions exist in complexes 1 and 2 resulting in two- and three-dimensional molecular arrangements, and the parallel arrangement of the ligand in the crystal of complex 3 resulted in a close inter- and intramolecular pi-pi interactions. Investigation of the crystals, as well as an amorphous thin film and powder of 3, by photoluminescence (PL) allowed the effect of the molecular packing on the emission properties to be elucidated. Furthermore, the electroluminescent (EL) properties of 3 were examined by fabricating a multilayer device with structure of [ITO/NPB/(ZnL)(n)/Alq3/LiF/Al] (NPB = N,N'-bis(alpha-naphthyl)-N,N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine, Alq3 = tris(8-hydroxyquinolinato)aluminum).

Journal Article↗
PubMed2006

Multipotent antioxidants: from screening to design.

Free-radicals play an important role in the pathogenesis of many diseases, accounting for continuing interest in the identification and development of novel antioxidants that prevent radical-induced damage. To develop more-powerful weapons that address complex diseases in which free-radicals might be significant, but not exclusive drivers, antioxidants that also have other pharmacological effects are desired. To obtain multipotent antioxidants, one can screen drug collections and/or natural-product libraries, or couple an antioxidant group with other pharmacophores. It is interesting to note that most rationally designed multifunctional antioxidants are structurally different from their naturally occurring counterparts. Therefore, nature's design strategy provides important clues as to how the design concept for multipotent antioxidants can be improved.

Animals↗
PubMed2006

Genetic analysis and histological study of red seed in rice.

Reciprocal crosses between red and achromatic rice revealed that the seed color of F1 was determined by its female parent. According to the seed color and plant segregation ratio of F1, F2, and F3 generations, the red phenotype of red double-haploid seed was determined by a dominant, monogene with maternal effect. Histological study showed that the red pigments accumulated in the pericarp layer only. The assay of developmental timing of pigment accumulation showed that the red color accumulated from desiccation stage to perfectly maturation stage of the seeds.

DNA, Plant↗
PubMed2006

CvP-bias as an index to predict the life style of last common ancestor.

CvP-bias (difference between proportions of charged and polar non-charged amino acids) has been recognized as an efficient criterion to distinguish hyperthermophiles from mesothermophiles. By analyzing the CvP-biases of seven barophiles's proteomes, we reveal that this criterion still works for barophiles. As a result, CvP-bias criterion is applicable to disclosing some secrets in the lifestyles of the last common ancestor (LCA), no matter the LCA lived in deep sea or not, which is helpful to building a self-consistent model for the LCA.

Amino Acids↗
PubMed2006

[Long-term effects of early hyperbaric oxygen therapy on neonatal rats with hypoxic-ischemic brain damage].

OBJECTIVE: The application and therapeutic effect of hyperbaric oxygen (HBO) in hypoxic-ischemic brain damage (HIBD) remains controversial. Previous studies have focused on the early pathological and biochemical outcomes and there is a lack of long-term functional evaluation. This study was designed to evaluate the long-term pathological and behavioral changes of early HBO therapy on neonatal rats with HIBD. METHODS: Postnatal 7 days (PD7) rat pups were randomly assigned into Control (n=18), HIBD (n=17) and HBO treatment groups (n=17). HIBD was induced by ligating the left common carotid, followed by 2 hrs hypoxia exposure in the HIBD and HBO treatment groups. The Control group was sham-operated and was not subjected to hypoxia exposure. The HBO therapy with 2 atmosphere absolutes began 0.5-1 hr after HIBD in the HIBD treatment group, once daily for 2 days. The spatial learning and memory ability were evaluated by the Morris water maze test at PD37 to PD41. The morphological and histological changes of the brain, including brain weight, survival neurons, AchE positive unit and NOS positive neurons in hippocampal CA1 region, were detected at PD42. RESULTS: The rats in the HIBD group displayed significant morphological and histological deficits, as well as severe spatial learning and memory disability. In the Morris water maze test, the mean escape latency were longer (56.35 +/- 22.37 s vs 23.07 +/- 16.28 s; P < 0.05) and the probe time and probe length were shorter in the HIBD group (29.29 +/- 6.06 s vs 51.21 +/- 4.59 s and 548 +/- 92 cm vs 989 +/- 101 cm; both P < 0.05) compared with the Control group. The left brain weight in the HIBD group was lighter than that in the Control group (0.601 +/- 0.59 g vs 0.984 +/- 0.18 g; P < 0.05). The survival neurons in the hippocampal CA1 region were less (100 +/- 27/mm vs 183 +/- 8/mm; P < 0.05), as well as the AchE-positive unit and NOS-positive neurons (18.50 +/- 2.24% vs 27.50 +/- 2.18% and 19.25 +/- 4.33 vs 33.75 +/- 5.57 respectively; P < 0.05) after HIBD. Early HBO treatment improved the abilities of spatial learning and alleviated the morphological and histological damage. The mean escape latency (39.17 +/- 21.20 s) was shortened, the probe time (36.84 +/- 4.36 s) and the probe length (686 +/- 76 cm) were longer, and the brain weight (0.768 +/- 0.85 g), the survival neurons (133 +/- 25/mm) and the AchE-positive unit (21.94 +/- 2.73%) increased significantly compared with those of the HIBD group (P < 0.05). CONCLUSIONS: Early HBO treatment resulted in a protective effect against HIBD-induced long-term brain morphological and histological deficits and spatial learning and memory disability.

Acetylcholinesterase↗
PubMed2005

Anion of hypericin is crucial to understanding the photosensitive features of the pigment.

Photosensitive behaviors of hypericin (HYP) have attracted much attention, because of HYP's great potential in photodynamic therapy. It has been found that HYP differs from homologous pigments, such as hypocrellin A (HA), in photosensitive features. For instance, despite the comparable triplet state quantum yields, HYP holds a much lower singlet oxygen yield than HA. To understand the unique photosensitive behaviors of HYP, time-dependent density functional theory is employed to calculate a series of excited-state properties of HYP and its anion (dominant in polar solvents), which are then compared with excited-state properties of HA. It is revealed that the stronger electron-donating power of HYP anion than that of HA is responsible for the HYP's photosensitive features.

Anions↗
PubMed2005

One-compound-multiple-targets strategy to combat Alzheimer's disease.

The present one-drug-one-target paradigm in drug discovery has been considered partially responsible for the more-funding-less-drug predicament in modern pharmaceutical industry. To hit the multiple targets implicated in complex diseases, two strategies, based on multicomponent or single-ingredient, are conceivable. Although the latter is more difficult to be fulfilled than the former, the recent progress made in the fight against Alzheimer's disease (AD) has brought us the first light of success of the latter strategy. In this review, both synthetic and natural multipotent agents are described, which hit two or more targets implicated in AD, e.g., acetylcholinesterase, monoamine oxidase, amyloid-beta, tau protein, metal ions and reactive oxygen species. Nevertheless, due to the potential risks in safety, absorbability and pharmacokinetics of synthetic multipotent agents, natural counterparts seem more promising in the future development.

Alzheimer Disease↗
PubMed2005

Evaluation of a new copper(II)-curcumin complex as superoxide dismutase mimic and its free radical reactions.

A mononuclear (1:1) copper complex of curcumin, a phytochemical from turmeric, was synthesized and examined for its superoxide dismutase (SOD) activity. The complex was characterized by elemental analysis, IR, NMR, UV-VIS, EPR, mass spectroscopic methods and TG-DTA, from which it was found that a copper atom is coordinated through the keto-enol group of curcumin along with one acetate group and one water molecule. Cyclic voltammetric studies of the complex showed a reversible Cu(2+)/Cu(+) couple with a potential of 0.402 V vs NHE. The Cu(II)-curcumin complex is soluble in lipids and DMSO, and insoluble in water. It scavenges superoxide radicals with a rate constant of 1.97 x 10(5) M(-1) s(-1) in DMSO determined by stopped-flow spectrometer. Subsequent to the reaction with superoxide radicals, the complex was found to be regenerated completely, indicating catalytic activity in neutralizing superoxide radicals. Complete regeneration of the complex was observed, even when the stoichiometry of superoxide radicals was 10 times more than that of the complex. This was further confirmed by EPR monitoring of superoxide radicals. The SOD mimicking activity of the complex was determined by xanthine/xanthine oxidase assay, from which it has been found that 5 microg of the complex is equivalent to 1 unit of SOD. The complex inhibits radiation-induced lipid peroxidation and shows radical-scavenging ability. It reacts with DPPH radicals with rate constant 10 times less than that of curcumin. Pulse radiolysis-induced one-electron oxidation of the complex by azide radicals in TX-100 micellar solutions produced strongly absorbing ( approximately 500 nm) phenoxyl radicals, indicating that the phenolic moiety of curcumin remained intact on complexation with copper. The results confirm that the new Cu(II)-curcumin complex possesses SOD activity, free radical neutralizing ability, and antioxidant potential. Quantum chemical calculations with density functional theory have been performed to support the experimental observations.

Antioxidants↗
PubMed2005

Unexpected amino acid composition of modern Reptilia and its implications in molecular mechanisms of dinosaur extinction.

Dinosaur extinction is a great challenge to evolutionary biology. Although accumulating evidence suggests that an abrupt change of environment, such as a long period of low temperature induced by asteroid hit or other disasters, may be responsible for dinosaur extinction, little is known about the underlying molecular mechanisms. By analyzing the amino acid compositions of 13 biological classes, we found that the charged amino acid content of modern Reptilia, the sibling of dinosaur, is strikingly different from those of other classes, which inspires us to propose a possible molecular mechanism for dinosaur extinction.

Amino Acid Sequence↗