Biomedical subjects

Guang Wu

Publications and source records attributed to Guang Wu.

At least 37 records · Page 2Linked to original sources

PubMed2004

Determination of sensitive positions to mutations in human p53 protein.

Over last several years, we demonstrated that the mutations are more likely to occur at randomly unpredictable amino acid pairs in a protein. We therefore can in principle predict the amino acid pairs sensitive to the future mutations in a protein. However, we still need to predict the positions at which the sensitive amino acid pairs are located in a protein. In this study, we use a probabilistic approach to analyze the effect of 191 mutations in human p53 protein and can approximately estimate the sensitive positions to mutations in human p53 protein.

Humans↗

PubMed2004

Determination of amino acid pairs sensitive to variants in human copper-transporting ATPase 2.

In this study, we use our probabilistic approach to analyze the amino acid pairs in human copper-transporting ATPase 2 (ATP7B) in order to determine which amino acid pairs are more sensitive to 125 variants from missense mutant human ATP7B. The results show 97.6% of 125 variants occur at randomly unpredictable amino acid pairs, which account for 80.9% of amino acid pairs in ATP7B, and the chance of occurring of variant is about 9 times higher in randomly unpredictable amino acid pairs than in predictable pairs. Thus, the randomly unpredictable amino acid pairs are more sensitive to variants in human ATP7B.

Adenosine Triphosphatases↗

PubMed2004

Geometry changes of a Cu(I) phenanthroline complex on photoexcitation in a confining medium by time-resolved X-ray diffraction.

Using a stroboscopic technique, in which the molecule is repeatedly excited and the structural change is probed more than 5000 times per second immediately after excitation, we performed a 16 K time-resolved single-crystal study of the microsecond lifetime triplet state of the Cu(I)phenanthroline derivative[Cu(I)(dmp)(dppe)][PF6] (dppe = 1,2-bis(diphenylphosphino)ethane). The geometry changes on excitation differ for the two symmetry-independent molecules, but are in the same direction as calculated for an isolated reference molecule, although the flattening distortion in the crystal is significantly smaller, implying that the reorganization energy is greatly affected by the confining medium.

Journal Article↗

PubMed2004

Fate of 130 hemagglutinins from different influenza A viruses.

In this study, we use our probabilistic models to analyze 130 hemagglutinins from different influenza A virus in order to gain the insight into their fate. The results provide three lines of evidence regarding the H5, H6, and H9 hemagglutinins: (i) the H5 hemagglutinins are more sensitive to mutations, this is the current state of the H5, H6, and H9 hemagglutinins; (ii) the H5 hemagglutinins had experienced more mutations in the past, this is the history of the H5, H6, and H9 hemagglutinins; and (iii) the H6 hemagglutinins has a bigger potential towards future mutations, this is the future of the H5, H6, and H9 hemagglutinins. Furthermore, this study gives two clues on the mutation tendency that is a degeneration process and the species susceptibility that is the chickens and ducks.

Hemagglutinins↗

PubMed2004

Potential targets for anti-SARS drugs in the structural proteins from SARS related coronavirus.

This is a further study on the severe acute respiratory syndrome (SARS) using the probabilistic models. The purpose was to define the potential targets for anti-SARS drugs in the structural proteins from human SARS related coronavirus (SARS-CoV) while knowing little about the functional sites and possible mutations in these proteins. From a probabilistic viewpoint, we can theoretically select the amino acid pairs as potential candidates for anti-SARS drugs. These candidates have a greater chance of colliding with anti-SARS drugs, are more likely to link with the protein functions and are less vulnerable to mutations.

Antiviral Agents↗

PubMed2004

Transcriptional regulation of cardiac sarcoplasmic reticulum calcium-ATPase gene during the progression of sepsis.

Changes in sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) gene expression in the rat heart during different phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). Septic rats were divided into two groups: the early hyperdynamic (9 h after CLP, early sepsis) and the late hypodynamic (18 h after CLP; late sepsis) groups. Western blot analyses reveal that SERCA2a protein level remained unaltered during early sepsis but was decreased by 59% during late sepsis. Northern blot analyses show that the steady-state level of SERCA2a mRNA stayed unchanged during the early phase but was decreased by 43% during the late phase of sepsis. Nuclear runoff assays show that the transcription rate of SERCA2a gene transcript remained unaffected during early sepsis but was decreased by 34% during late sepsis. The actinomycin D pulse-chase studies indicate that the half-life of SERCA2a mRNA was unaffected during the early and the late phases of sepsis. These findings demonstrate that during the early phase of sepsis, the protein level, the mRNA abundance, and the transcription rate of SERCA2a remained unaltered, whereas during the late phase of sepsis, the rate of transcription of SERCA2a was decreased, and the decreased transcription rate was associated with decreases in SERCA2a mRNA abundance and SERCA2a protein level in the rat heart. Based on these data, it is concluded that SERCA2a gene expression decreased during the late phase of sepsis in the rat heart and that the decreased expression was regulated at the transcriptional level.

Animals↗

PubMed2003

Determination of amino acid pairs in human p53 protein sensitive to mutations/variants by means of a random approach.

This is the continuation of our studies using random approaches to analyse the p53 protein family. In this data-based theoretical analysis, we use the random approach to analyse the amino acid pairs in human p53 protein in order to determine which amino acid pairs are more sensitive to 190 human p53 mutations/variants. The rationale of this study is based on our hypothesis and findings that a harmful mutation is more likely to occur at randomly unpredictable amino acid pairs, and a harmless mutation is more likely to occur at randomly predictable amino acid pairs. This is because we argue that the randomly predictable amino acid pairs should not be deliberately evolved, whereas the randomly unpredictable amino acid pairs should be deliberately evolved with a connection to protein function. The results show, for example, that 93.16% of 190 mutations/variants occur at randomly unpredictable amino acid pairs. Thus, the randomly unpredictable amino acid pairs are more sensitive to mutations/variants in human p53 protein. The results also suggest that the human p53 protein has a tendency for the occurrence of mutation/variants.

Amino Acids↗

PubMed2003

Investigation of Zr-C, Zr-N, and potential agostic interactions in an organozirconium complex by experimental electron density analysis.

The crystal structure and electron density (ED) distribution of an imine coupling product with an open zirconocene, Zr(2,4-C(7)H(11))[(i-Pr)NCHPhCH(2)CMe=CHCMe=CH(2)] (C(7)H(11) = dimethylpentadienyl), have been derived from accurate synchrotron X-ray diffraction measurements. The molecular structure reveals asymmetric coordination of Zr by the pentadienyl (2,4-C(7)H(11)) ligand ( = 2.56(6) A), the butadiene fragment ( = 2.43(5) A), and the amide nitrogen atom (Zr-N = 2.0312(5) A) of the second ligand. The study of the ED and its topological analysis affords new insight into the bonding and electronic structure of the title zirconium complex. The interactions between the metal center and the ligands are represented by a Zr-N bond path and one Zr-C bond path with each of the pentadienyl and butadiene moieties, contrary to the usually depicted global metal-ligand bonding. The butadiene and pentadienyl groups exhibit a polarization of the corresponding pi-like ED in the C-Zr directions, indicating that the whole conjugated systems are nonetheless involved. The 4d atomic orbitals of Zr exhibit unusual populations according to ligand field considerations, which reveal a high degree of sigma-donation from the conjugated pi systems of both ligands. As deduced from numerical integration over the topologically defined atomic basins, the Zr to ligand charge transfer is 1.48 e to the C(17)NH(24) ligand and 0.68 e to dimethylpentadienyl. Topological analysis of a short intramolecular Zr.(C,H) contact provides no indication of the presence of agostic interactions, despite a small Zr-N-C angle of 102.87(4) degrees. Thus, no bond path and BCP (bond critical point) of the ED are found in the Zr.(C,H) region, which would have provided evidence for such direct interactions, nor is there any evidence for charge accumulation between the Zr and H atoms, or for lengthening of the C-H bond involved in the putative interaction. These characteristics, similar to those in other distorted situations, may be common for other electron-deficient d(0) complexes.

Journal Article↗

PubMed2003

Prediction of amino acid pairs sensitive to mutations in the spike protein from SARS related coronavirus.

In this study, we analyzed the amino acid pairs affected by mutations in two spike proteins from human coronavirus strains 229E and OC43 by means of random analysis in order to gain some insight into the possible mutations in the spike protein from SARS-CoV. The results demonstrate that the randomly unpredictable amino acid pairs are more sensitive to the mutations. The larger is the difference between actual and predicted frequencies, the higher is the chance of mutation occurring. The effect induced by mutations is to reduce the difference between actual and predicted frequencies. The amino acid pairs whose actual frequencies are larger than their predicted frequencies are more likely to be targeted by mutations, whereas the amino acid pairs whose actual frequencies are smaller than their predicted frequencies are more likely to be formed after mutations. These findings are identical to our several recent studies, i.e. the mutations represent a process of degeneration inducing human diseases.

Amino Acids↗

PubMed2003

Analysis of amino acid pairs sensitive to variants in human collagen alpha5(IV) chain precursor by means of a random approach.

In this data-based theoretical analysis, we use the random approach to analyze the amino acid pairs in 5(IV) chain precursor (CA54) in order to determine which amino acid pairs are more sensitive to 151 variants from missense mutant human CA54 protein. The rationale of this study is based on our hypothesis and previous findings that harmful variance is more likely to occur at randomly unpredictable amino acid pair position rather than at randomly predictable positions. This is reasonable to argue as randomly predictable amino acid pairs are less likely to be deliberately evolved, whereas randomly unpredictable amino acid pairs are probably deliberately evolved in connection with protein function. The results show that all 151 variants occurred at randomly unpredictable amino acid pairs and the chance of a variant occurring is markedly higher in randomly unpredictable amino acid pairs than in predictable pairs. Thus, randomly unpredictable amino acid pairs are more sensitive to variance in human CA54. The results also suggest that the human CA54 protein has a natural tendency towards variants.

Amino Acids↗

PubMed2003

Determination of amino acid pairs sensitive to variants in human beta-glucocerebrosidase by means of a random approach.

In this data-based theoretical analysis, we use the random approach to analyse the amino acid pairs in human beta-glucocerebrosidase in order to determine which amino acid pairs are more sensitive to 109 variants from missense mutant human glucocerebrosidase. The rationale of this study is based on our hypothesis and findings that the harmful variants are more likely to occur at randomly unpredictable amino acid pairs and the non-harmful variants are more likely to occur at randomly predictable amino acid pairs. This is because we argue that the randomly predictable amino acid pairs should not be deliberately evolved, whereas the randomly unpredictable amino acid pairs should be deliberately evolved with connection of protein function. The results show, for example, that 93.58% of 109 variants occur at randomly unpredictable amino acid pairs, which account for 71.40% of amino acid pairs in glucocerebrosidase, and the chance of occurrence of the variant is about 4.4 times higher in randomly unpredictable amino acid pairs than in predictable pairs. Hence the randomly unpredictable amino acid pairs are more sensitive to variants in human glucocerebrosidase. The results also suggest that human glucocerebrosidase has a natural tendency to variants.

Amino Acids↗

PubMed2002

Application of charge density methods to a protein model compound: calculation of Coulombic intermolecular interaction energies from the experimental charge density.

A combined experimental and theoretical charge density study of the pentapeptide Boc-Gln-d-Iva-Hyp-Ala-Phol (Boc, butoxycarbonyl; Gln, glutamine; Iva, isovaline; Hyp, hydroxyproline; Ala, ethylalanine; Phol, phenylalaninol) is described. The experimental analysis, based on synchrotron x-ray data collected at 20 K, is combined with ab initio theoretical calculations. The topologies of the experimental and theoretical densities are analyzed in terms of the atoms in molecules quantum theory. Topological parameters, including atomic charges and higher moments integrated over the atomic basins, have been evaluated with the program topxd and are used to calculate the electrostatic interactions between the molecules in the crystal. The interaction energies obtained after adding dispersive and repulsive van der Waals contributions agree quite well with those based on M-B3LYP/6-31G** dimer calculations for two of the three dimers in the crystal, whereas for the third a larger stabilization is obtained than predicted by the calculation. The agreement with theory is significantly better than that obtained with multipole moments derived directly from the aspherical atom refinement. The convergence of the interaction as a function of addition of successively higher moments up to and including hexadecapoles (l = 4) is found to be within 2-3 kJ/mol. Although shortcomings of both the theoretical and experimental procedures are pointed out, the agreement obtained supports the potential of the experimental method for the evaluation of interactions in larger biologically relevant molecules.

Biophysical Phenomena↗

PubMed2002

Excited-state structure by time-resolved X-ray diffraction.

X-ray crystallography has traditionally been limited to the study of the ground-state structure of molecules and solids. Recent technical advances are removing this limitation as demonstrated here by a time-resolved stroboscopic study of the photo-induced 50 micros lifetime excited triplet state of the [Pt(2)(pop)(4)](4-)ion [pop = pyrophosphate, (H(2)P(2)O(5))(2-)], performed at helium temperatures with synchrotron radiation. The shortening of the Pt-Pt bond by 0.28(9)A upon excitation is compatible with the proposed mechanism involving promotion of a Pt-Pt antibonding dsigma* electron to a weakly bonding p orbital. The contraction is accompanied by a 3 degree molecular rotation. The time-resolved diffraction technique described here is applicable to reversible light-driven processes in the crystalline solid state.

Journal Article↗

PubMed2002

Analysis of distributions of amino acids in the primary structure of tumor suppressor p53 family according to the random mechanism.

It is well known that the evolutionary process leads to the majority of amino acids clustering in some regions rather than being homogenously distributed along a protein. Among numerous factors affecting the evolutionary process is chance, whose impact therefore should be present in a protein primary structure. The issue of how to measure the random distribution of amino acids in a primary structure is of importance for the understanding of protein structure and functions. In this study, we use the random principle as a tool to analyze and compare the distributions of amino acids in the primary structure of the p53 protein family. The results, for example, show that the amino acids are distributed more randomly in mouse p53 and less randomly in common tree shrew p53, the distribution ranks of amino acids are relatively lower in the functional regions (about 0.5 on average) than in the whole sequences (about 1.2 on average) except for mouse p53. From the probabilistic distribution view, the composition of human p53 is relatively stable in the functional regions rather than in the whole sequence, which may suggest one of the potential effects on the mutations inducing human cancers. In general, we can use the distribution probability to present quantitatively a type of distribution of amino acids in a protein, to compare quantitatively the magnitude of clusters between different proteins and to track the effect of chance on the evolutionary process.

Amino Acids↗

PubMed2002

Estimation of amino acid pairs sensitive to variants in human phenylalanine hydroxylase protein by means of a random approach.

In this data-based theoretical analysis, we use a random approach to estimate amino acid pairs in human phenylalanine 4-hydroxylase (PAH) protein in order to determine which amino acid pairs are more sensitive to 187 variants in human PAH protein. The rationale of this study is based on our hypothesis and previous findings that the harmful variants are more likely to occur at randomly unpredictable amino acid pairs rather than at randomly predictable pairs. This is reasonable to argue as randomly predictable amino acid pairs are less likely to be deliberately evolved, whereas randomly unpredictable amino acid pairs are probably deliberately evolved in connection with protein function. 94.12% of 187 variants occurred at randomly unpredictable amino acid pairs, which accounted for 71.84% of 451 amino acid pairs in human PAH protein. The chance of a variant occurring is five times higher in randomly unpredictable amino acid pairs than in predictable pairs. Thus, randomly unpredictable amino acid pairs are more sensitive to variance in human PAH protein. The results also suggest that the human PAH protein has a natural tendency towards variants.

Amino Acids↗

PubMed2002

Analysis of distributions of amino acids in the primary structure of apoptosis regulator Bcl-2 family according to the random mechanism.

It is no long a question whether the process of evolution is affected by chance, but is to what extent. The random analysis can throw light on the underlying reasoning for the primary structure of proteins. The study on the Bcl-2 family shows that the rank per amino acid increases 93% in bovine than in chicken and rat, which indicates that the effect of chance has more impact on the evolutionary process of chicken and rat Bcl-2 and less impact on bovine Bcl-2. About one fourth of types of amino acids distribute in the highest probabilistic way in the Bcl-2 family. These phenomena are striking in four BH regions where vast majority of amino acids occur with the probabilistically simplest distribution. Mutations and variants can lead to the increased and/or decreased distribution probabilities of amino acids. Mutations 1, 2 and variant 3 target the rank increased in both affected amino acids. By contrast variants 1 and 2 lead to the rank decreased in both affected amino acids. In mutations 3 and 4, the affected amino acids change their ranks to opposite directions, i.e. the rank is lower in replaced amino acid and higher in replacing one. Using our random approaches as quantitative tools, we can measure, compare and explain the primary structures of proteins.

Amino Acids↗

PubMed2002

Determination of amino acid pairs sensitive to variants in human low-density lipoprotein receptor precursor by means of a random approach.

In this data-based theoretical analysis, we use the random approach to analyse the amino acid pairs in human low-density lipoprotein receptor (LDL receptor) precursor in order to determine which amino acid pairs are more sensitive to 127 variants from missense mutant human LDL receptor. The rationale of this study is based on our hypothesis and findings that the harmful variants are more likely to occur at randomly unpredictable amino acid pairs, the unharmful variants are more likely to occur at randomly predictable amino acid pairs. This is because we argue that the randomly predictable amino acid pairs should not be deliberately evolved, whereas the randomly unpredictable amino acid pairs should be deliberately evolved with connection of protein function. The results show, for examples, 96.06% of 127 variants occur at randomly unpredictable amino acid pairs, which account for 80.44% of amino acid pairs in LDL receptor, and the chance of occurring of variant is about five times higher in randomly unpredictable amino acid pairs than in predictable pairs. Thus, the randomly unpredictable amino acid pairs are more sensitive to variants in human LDL receptor. The results also suggest that the human LDL receptor has the natural tendency to variants.

Amino Acids↗

PubMed1998

Multitemperature Resonance-Diffraction and Structural Study of the Mixed-Valence Complex [Fe(3)O(OOCC(CH(3))(3))(6)(C(5)H(5)N)(3)].

The Fe-O and Fe-N bond lengths at two iron sites of the mixed-valence complex [Fe(3)O(OOCC(CH(3))(3))(6)(C(5)H(5)N)(3)] show a pronounced temperature dependence; the bonds from two of the Fe atoms to the central oxygen atoms vary by more than 0.10 Å on cooling to 10 K whereas the bond from the third iron atom is essentially invariant. The variation is such that the longest Fe-O bonds at ambient temperature are the shorter ones at 10 K, with the crossover occurring at about 90 K. The bonds to the axial pyridine ligand show the opposite dependence. The variation is attributed to an equilibrium between different configurations, which interconvert through vibronic coupling, a process that involves electron transfer between the metal atoms. The position of the absorption edge for each of the iron atoms has been determined by resonance-diffraction experiments at the Fe K edge, performed at four different temperatures. At each temperature, the order of the absorption edges corresponds to that of the experimentally determined bond lengths. The crossover near 90 K is confirmed by the resonance experiments. The absorption-edge positions are related to the formal oxidation state by calibration with reference complexes of known oxidation state. The experiments demonstrate the close relation between the changes in coordination geometry and the oxidation states of the iron atoms.

Journal Article↗