Long-Range Conformational Response of a PDZ Domain to Ligand Binding and Release: A Molecular Dynamics Study

The binding of a ligand to a protein may induce long-range structural or dynamical changes in the biomacromolecule even at sites physically well separated from the binding pocket. A system for which such behavior has been widely discussed is the PDZ2 domain of human tyrosine phosphatase 1E. Here, we present results from equilibrium trajectories of the PDZ2 domain in the free and ligand-bound state, as well as nonequilibrium simulations of the relaxation of PDZ2 after removal of its peptide ligand. The study reveals changes in inter-residue contacts, backbone dihedral angles, and C_α positions upon ligand release. Our findings show a long-range conformational response of the PDZ2 domain to ligand release in the form of a collective shift of the secondary structure elements α₂, β₂, β₃, α₁-β₄, and the C terminal loop relative to the rest of the protein away from the N-terminus, and a shift of the loops β₂-β₃ and β₁-β₂ in the opposite direction. The shifts lead to conformational changes in the backbone, especially in the β₂-β₃ loop but also in the β₅-α₂ and the α₂-β₆ loop, and are accompanied by changes of inter-residue contacts mainly within the β₂-β₃ loop as well as between the α₂ helix and other segments. The residues showing substantial changes of inter-residue contacts, backbone conformations, or C_α positions are considered “key residues” for the long-range conformational response of PDZ2. By comparing these residues with various sets of residues highlighted by previous studies of PDZ2, we investigate the statistical correlation of the various approaches. Interestingly, we find a considerable correlation of our findings with several works considering structural changes but no significant correlations with approaches considering energy flow or networks based on inter-residue energies

Additional file 5: of Tau GSTs involved in regulation of leaf abscission by comparison the gene profiling of MeGSTs in various abscission-promoting treatments in cassava abscission zones

Data 4. Five clusters of the cassava GST genes expressed in abscission zones in ethylene treatment or drought treatment induced leaf abscission by Hierarchical clustering analysis. (XLS 36 kb

Additional file 2: of Tau GSTs involved in regulation of leaf abscission by comparison the gene profiling of MeGSTs in various abscission-promoting treatments in cassava abscission zones

Data 2. The accession numbers of GSTs in cassava. (XLSX 20 kb

MOESM1 of Identification of novel tylosin analogues generated by a wblA disruption mutant of Streptomyces ansochromogenes

Additional file 1. Figure S1. NMR Spectra of compound 1. (A) Summary of key correlations between protons and carbons in compound 1 based on NMR spectroscopic data. (B) 1H-1H COSY spectrum of compound 1. (C) 1H-13C HSQC spectrum of compound 1. (D) 1H-13C HMBC spectrum of compound 1. Figure S2. NMR Spectra of compound 2. (A) Summary of key correlations between protons and carbons in compound 2 based on NMR spectroscopic data. (B) 1H-1H COSY spectrum of compound 2. (C) 1H-13C HSQC spectrum of compound 2. (D) 1H-13C HMBC spectrum of compound 2. Table S1. Antimicrobial activities of fermentation broth from S. ansochromogenes 7100 and ΔwblA by agar diffusion assays

Additional file 1: of Tau GSTs involved in regulation of leaf abscission by comparison the gene profiling of MeGSTs in various abscission-promoting treatments in cassava abscission zones

Data 1. Primers used in qRT-PCR analysis. (XLS 39 kb

Additional file 3: of Tau GSTs involved in regulation of leaf abscission by comparison the gene profiling of MeGSTs in various abscission-promoting treatments in cassava abscission zones

Figure S1. Sequence logos for conserved motifs identified in MeGSTs by MEME analysis. (JPG 1160 kb

Mammary Fat of Breast Cancer: Gene Expression Profiling and Functional Characterization

<div><p>Mammary fat is the main composition of breast, and is the most probable candidate to affect tumor behavior because the fat produces hormones, growth factors and adipokines, a heterogeneous group of signaling molecules. Gene expression profiling and functional characterization of mammary fat in Chinese women has not been reported. Thus, we collected the mammary fat tissues adjacent to breast tumors from 60 subjects, among which 30 subjects had breast cancer and 30 had benign lesions. We isolated and cultured the stromal vascular cell fraction from mammary fat. The expression of genes related to adipose function (including adipogenesis and secretion) was detected at both the tissue and the cellular level. We also studied mammary fat browning. The results indicated that fat tissue close to malignant and benign lesions exhibited distinctive gene expression profiles and functional characteristics. Although the mammary fat of breast tumors atrophied, it secreted tumor growth stimulatory factors. Browning of mammary fat was observed and browning activity of fat close to malignant breast tumors was greater than that close to benign lesions. Understanding the diversity between these two fat depots may possibly help us improve our understanding of breast cancer pathogenesis and find the key to unlock new anticancer therapies.</p></div

TiO₂ Nanoparticles-Functionalized N‑Doped Graphene with Superior Interfacial Contact and Enhanced Charge Separation for Photocatalytic Hydrogen Generation

Titanium dioxide (TiO₂) nanoparticles-functionalized N-doped graphene (NGR) composites (NGR/TiO₂) were prepared through solvothermal treatment approach using exfoliated NGR and tetrabutyl titanate as the staring materials. The composites were characterized by transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, UV–vis diffuse reflectance spectra, photoelectrochemical, and electrochemical measurements. Nitrogen doping provides favorable nucleation and anchor sites for TiO₂ nanocrystals formation on NGR sheets, helping to form an intimate interfacial contact between NGR and TiO₂ nanoparticles. Moreover, NGR has higher electrical conductivity than the reduced graphene oxide (RGO) due to the recovery of the sp² graphite network and decrease of defects, resulting in more effective charge transfer and charge separation in the NGR/TiO₂ composite. NGR/TiO₂ nanocomposite demonstrated a higher photocatalytic activity for hydrogen production as compared to its counterpart, TiO₂-functionalized RGO composite (RGO/TiO₂). This work provides new insights to design new more efficient graphene-based nanocomposite photocatalysts for solar energy conversion

The Shared Crosstalk of Multiple Pathways Involved in the Inflammation between Rheumatoid Arthritis and Coronary Artery Disease Based on a Digital Gene Expression Profile

<div><p>Rheumatoid arthritis (RA) and coronary artery disease (CAD) are both complex inflammatory diseases, and an increased prevalence of CAD and a high rate of mortality have been observed in RA patients. But the molecular mechanism of inflammation that is shared between the two disorders is unclear. High-throughput techniques, such as transcriptome analysis, are becoming important tools for genetic biomarker discovery in highly complex biological samples, which is critical for the diagnosis, prognosis, and treatment of disease. In the present study, we reported one type of transcriptome analysis method: digital gene expression profiling of peripheral blood mononuclear cells of 10 RA patients, 10 CAD patients and 10 healthy people. In all, 213 and 152 differently expressed genes (DEGs) were identified in RA patients compared with normal controls (RA <i>vs.</i> normal) and CAD patients compared with normal controls (CAD <i>vs.</i> normal), respectively, with 73 shared DEGs between them. Using this technique in combination with Ingenuity Pathways Analysis software, the effects on inflammation of four shared canonical pathways, three shared activated predicted upstream regulators and three shared molecular interaction networks were identified and explored. These shared molecular mechanisms may provide the genetic basis and potential targets for optimizing the application of current drugs to more effectively treat these diseases simultaneously and for preventing one when the other is diagnosed.</p></div

Structural Evolutions and Crystal Field Characterizations of Tm-Doped YAlO₃: New Theoretical Insights

The recent renaissance of the use of rare-earth-doped yttrium orthoaluminate as an ideal laser material has generated significant interest; however, the unique structural features underlying many of its outstanding optical properties still require elucidation. To solve this intriguing problem, we performed a systematic first-principles study; the results of the study reveal a new stable phase for Tm³⁺-doped YAlO₃ (YAP), of monoclinic <i>Pm</i> symmetry, with an 80-atom per unit cell. An unbiased CALYPSO structure search indicates that the Tm³⁺ impurity ion tends to substitute the position of Y³⁺ in the YAP crystal lattice. Electronic band structure calculations reveal that the insulated behaviors of YAP are significantly eliminated after doping the impure Tm³⁺ ions, as evidenced by the minor energy gap of about 0.4 eV, which is close to the band gap energy of a 2 μm emitter source. On the basis of our developed crystal-field theory method, the 4f¹² electronic structures and energies of Tm³⁺ ions in the YAP crystal are calculated. The theoretical results indicate that the electric-dipole-induced transition ³H₄ → ³H₅ is mainly responsible for producing the light wave at approximately 2.3 μm. The present results provide an essential understanding of the rare-earth-ion-doped lasing materials and serve as a practical tool for further exploration of such materials