Biomedical subjects

Yonghong Zhao

Publications and source records attributed to Yonghong Zhao.

8 recordsLinked to original sources

PubMed2006

The crystal structure of the E. coli stress protein YciF.

YciF is a protein that is up-regulated when bacteria experience stress conditions, and is highly conserved in a range of bacterial species. YciF has no known structure or biochemical function. To learn more about its potential molecular function and its role in the bacterial stress response, we solved the crystal structure of YciF at 2.0 Angstrom resolution by the multiple wavelength anomalous diffraction (MAD) technique. YciF is a dimer in solution, and forms a homodimer in the crystal asymmetric unit. The two monomers form a dimer with a molecular twofold axis, with a significant burial of solvent-accessible surface area. The protein is an all-alpha protein composed of five helices: a four-helix bundle, and a short additional helix at the dimer interface. The protein is structurally similar to portions of the diiron-containing proteins, rubrerythrin and the Bacillus anthracis Dlp-2.

Amino Acid Sequence↗

PubMed2006

Structure-function analysis of cytochromes P450 2B.

In the last 4 years, breakthroughs were made in the field of P450 2B (CYP2B) structure-function through determination of one ligand-free and two inhibitor-bound X-ray crystal structures of CYP2B4, which revealed many of the structural features required for binding ligands of different size and shape. Large conformational changes of several plastic regions of CYP2B4 can dramatically reshape the active site of the enzyme to fit the size and shape of the bound ligand without perturbing the overall P450 fold. Solution biophysical studies using isothermal titration calorimetry (ITC) have revealed the large difference in the thermodynamic parameters of CYP2B4 in binding inhibitors of different ring chemistry and side chains. Other studies have revealed that the effects of site-specific mutations on steady-state kinetic parameters and mechanism-based inactivation are often substrate dependent. These findings agree with the structural data that the enzymes adopt different conformations to bind various ligands. Thus, the substrate specificity of an individual enzyme is determined not only by active site residues but also non-active site residues that modulate conformational changes that are important for substrate access and rearrangement of the active site to accommodate the bound substrate.

Animals↗

PubMed2005

Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction.

To better understand ligand-induced structural transitions in cytochrome P450 2B4, protein-ligand interactions were investigated using a bulky inhibitor. Bifonazole, a broad spectrum antifungal agent, inhibits monooxygenase activity and induces a type II binding spectrum in 2B4dH(H226Y), a modified enzyme previously crystallized in the presence of 4-(4-chlorophenyl)imidazole (CPI). Isothermal titration calorimetry and tryptophan fluorescence quenching indicate no significant burial of protein apolar surface nor altered accessibility of Trp-121 upon bifonazole binding, in contrast to recent results with CPI. A 2.3 A crystal structure of 2B4-bifonazole reveals a novel open conformation with ligand bound in the active site, which is significantly different from either the U-shaped cleft of ligand-free 2B4 or the small active site pocket of 2B4-CPI. The O-shaped active site cleft of 2B4-bifonazole is widely open in the middle but narrow at the top. A bifonazole molecule occupies the bottom of the active site cleft, where helix I is bent approximately 15 degrees to accommodate the bulky ligand. The structure also defines unanticipated interactions between helix C residues and bifonazole, suggesting an important role of helix C in azole recognition by mammalian P450s. Comparison of the ligand-free 2B4 structure, the 2B4-CPI structure, and the 2B4-bifonazole structure identifies structurally plastic regions that undergo correlated conformational changes in response to ligand binding. The most plastic regions are putative membrane-binding motifs involved in substrate access or substrate binding. The results allow us to model the membrane-associated state of P450 and provide insight into how lipophilic substrates access the buried active site.

Antifungal Agents↗

PubMed2005

[The advance of experimental cell division biomechanics].

The advance of experimental cell division and proliferation in the field of cell biomechanics is presented in this paper. The emphasis is placed on the research in the mechanics mechanism of cleavage furrow and in the measurement of constricting force about cleavage furrow.

Biomechanical Phenomena↗

PubMed2004

Escherichia coli stress protein YciF: expression, crystallization and preliminary crystallographic analysis.

The Escherichia coli stress protein YciF was overexpressed and purified by three chromatographic steps. Crystals were obtained using ammonium sulfate as a precipitant. The YciF protein crystals diffracted beyond 2.25 A resolution using a rotating-anode X-ray source. The lattice type is rhombohedral, with unit-cell parameters a = b = 80.0, c = 131.03 A, alpha = beta = 90.0, gamma = 120.0 degrees. The crystal belongs to space group R32.

Amino Acid Sequence↗

PubMed2004

Expression, crystallization and preliminary crystallographic analysis of YciE, a stress protein from Escherichia coli.

The stress protein Escherichia coli YciE was overexpressed and purified in three chromatographic steps. Crystals were obtained using PEG 4000 as a precipitant. The YciE protein crystals diffracted to 3.0 A resolution using a rotating-anode X-ray source. The lattice type is rhombohedral, with unit-cell parameters a = b = 64.2, c = 167.9 A, alpha = beta = 90, gamma = 120 degrees. The crystal belongs to space group R32.

Crystallization↗

PubMed2004

[Partial middle turbinatectomy and folded for nasonsociliary neuralgia by transnasal endoscopic surgery].

OBJECTIVE: To explore into the feasibility and outcome of partial middle turbinetectomy and folded for nasociliary neuralgia by transnasal endoscopic surgery. METHOD: Forty patients with nasociliary neuralgia were treated by partial middle turbinatectomy and folded. RESULT: All patients have got sufficient of factory sulcus without hyposmia. The curable rate and the improve rate were 97.5% and 2.5%, respectively, with the total effective rate 100%. CONCLUSION: This procedure present an ideal effect. It is a safe, minimally invasive and efficient procedure for nasociliary neuralgia.

Adult↗

PubMed2003

The crystal structure of Escherichia coli heat shock protein YedU reveals three potential catalytic active sites.

The mRNA of Escherichia coli yedU gene is induced 31-fold upon heat shock. The 31-kD YedU protein, also calls Hsp31, is highly conserved in several human pathogens and has chaperone activity. We solved the crystal structure of YedU at 2.2 A resolution. YedU monomer has an alpha/beta/alpha sandwich domain and a small alpha/beta domain. YedU is a dimer in solution, and its crystal structure indicates that a significant amount of surface area is buried upon dimerization. There is an extended hydrophobic patch that crosses the dimer interface on the surface of the protein. This hydrophobic patch is likely the substrate-binding site responsible for the chaperone activity. The structure also reveals a potential protease-like catalytic triad composed of Cys184, His185, and Asp213, although no enzymatic activity could be identified. YedU coordinates a metal ion using His85, His122, and Glu90. This 2-His-1-carboxylate motif is present in carboxypeptidase A (a zinc enzyme), and a number of dioxygenases and hydroxylases that utilize iron as a cofactor, suggesting another potential function for YedU.

Amino Acid Motifs↗