Crystal structure of a class 3 aldehyde dehydrogenase at 2.6 A resolution.
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Aldehyde Dehydrogenase↗
Biomedical subjects
B C Wang
Publications and source records attributed to B C Wang.
Conserved residues in the aldehyde dehydrogenase family. Locations in the class 3 tertiary structure.
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Aldehyde Dehydrogenase↗
Plasma spraying of zirconia-reinforced hydroxyapatite composite coatings on titanium: part II: dissolution behaviour in simulated body fluid and bonding degradation.
The change of phase, morphology and bond strength of plasma sprayed hydroxyapatite (HA) coating and ZrO2/HA composite coatings immersed in simulated body fluid (SBF) for various periods of time was studied. X-ray diffractometry (XRD) and scanning electron microscopy (SEM) were used to identify the phase and observe the morphology of the coating surface before and after immersion. In addition, inductively coupled plasma emission spectroscopy (ICP) was used to measure the ion release rate of coatings in SBF for various periods of time. Observation of the morphology by SEM shows that the composite coating with the addition of ZrO2 in HA significantly reduced the dissolution rate of impurity phases in simulated body fluid. The argument was supported by measurement of Ca2+ ion concentration in SBF. During plasma spraying, less OH- ions were lost in a ZrO2-containing composite coating. This factor, together with the reduced effective surface of the ZrO2-containing HA coating, were attributed to the reduced dissolution rate of the composite coatings. All the plasma sprayed coatings degraded after immersion in SBF owing to dissolution of constituents in the coating, however, the addition of ZrO2 in HA improved the bonding strength of HA coating after immersion in SBF.
Journal Article↗
Plasma spraying of zirconia-reinforced hydroxyapatite composite coatings on titanium: part I: phase, microstructure and bonding strength.
Plasma-sprayed hydroxyapatite (HA) coatings applied to metal substrates can induce a direct chemical bond with bone and hence achieve biological fixation of the implant. However, the poor bonding strength between HA and substrate has been of concern to orthopaedists. In this study, two submicrometre ZrO2 powders stabilized with both 3 and 8 mol% Y2O3 (TZ3Y and TZ8Y, respectively) were incorporated in a plasma-sprayed HA coating on Ti-6Al-4V substrate to investigate the change in phase, microstructure and bonding strength. The results show that ZrO2 composite coatings contain more unmelted particles and greater porosity. During plasma spraying, ZrO2 reacts with the CaO in HA to form CaZrO3 and accelerates HA decomposition to alpha-TCP and Ca4P2O9. Nevertheless, bonding strength increases with increase of ZrO2 content in the range 0 to 10 wt% studied. The higher Y2O3-containing TZ8Y apparently exerts a greater strengthening effect than the lower Y2O3-containing TZ3Y.
Journal Article↗
The first structure of an aldehyde dehydrogenase reveals novel interactions between NAD and the Rossmann fold.
The first structure of an aldehyde dehydrogenase (ALDH) is described at 2.6 A resolution. Each subunit of the dimeric enzyme contains an NAD-binding domain, a catalytic domain and a bridging domain. At the interface of these domains is a 15 A long funnel-shaped passage with a 6 x 12 A opening leading to a putative catalytic pocket. A new mode of NAD binding, which differs substantially from the classic beta-alpha-beta binding mode associated with the 'Rossmann fold', is observed which we term the beta-alpha,beta mode. Sequence comparisons of the class 3 ALDH with other ALDHs indicate a similar polypeptide fold, novel NAD-binding mode and catalytic site for this family. A mechanism for enzymatic specificity and activity is postulated.
Aldehyde Dehydrogenase↗
The crystal structure of glutamine-binding protein from Escherichia coli.
The crystal structure of the glutamine-binding protein (GlnBP) from Escherichia coli in a ligand-free "open" conformational state has been determined by isomorphous replacement methods and refined to an R-value of 21.4% at 2.3 A resolution. There are two molecules in the asymmetric unit, related by pseudo 4-fold screw symmetry. The refined model consists of 3587 non-hydrogen atoms from 440 residues (two monomers), and 159 water molecules. The structure has root-mean-square deviations of 0.013 A from "ideal" bond lengths and 1.5 degrees from "ideal" bond angles. The GlnBP molecule has overall dimensions of approximately 60 A x 40 A x 35 A and is made up of two domains (termed large and small), which exhibit a similar supersecondary structure, linked by two antiparallel beta-strands. The small domain contains three alpha-helices and four parallel and one antiparallel beta-strands. The large domain is similar to the small domain but contains two additional alpha-helices and three more short antiparallel beta-strands. A comparison of the secondary structural motifs of GlnBP with those of other periplasmic binding proteins is discussed. A model of the "closed form" GlnBP-Gln complex has been proposed based on the crystal structures of the histidine-binding protein-His complex and "open form" GlnBP. This model has been successfully used as a search model in the crystal structure determination of the "closed form" GlnBP-Gln complex by molecular replacement methods. The model agrees remarkably well with the crystal structure of the Gln-GlnBP complex with root-mean-square deviation of 1.29 A. Our study shows that, at least in our case, it is possible to predict one conformational state of a periplasmic binding protein from another conformational state of the protein. The glutamine-binding pockets of the model and the crystal structure are compared and the modeling technique is described.
Amino Acid Sequence↗
Crystals of ligand-free bovine neurophysin II.
A modified neurophysin, des 1-6 bovine neurophysin II, has been crystallized in the absence of bound hormone or hormone analogue. These crystals represent the first crystals of ligand-free neurophysin, and are essential for understanding neurophysin-hormone recognition as well as hormone-induced neurophysin dimerization. The crystals diffract to beyond 1.8 A resolution, belong to space group P3(1)21 (or P3(2)21) with a = 48.86, c = 78.61 A, and contain one molecule per asymmetric unit.
Journal Article↗
Crystal structure of the neurophysin-oxytocin complex.
The first crystal structure of the pituitary hormone oxytocin complexed with its carrier protein neurophysin has been determined and refined to 3.0 A resolution. The hormone-binding site is located at the end of a 3(10)-helix and involves residues from both domains of each monomer. Hormone residues Tyr 2, which is buried deep in the binding pocket, and Cys 1 have been confirmed as the key residues involved in neurophysin-hormone recognition. We have compared the bound oxytocin observed in the neurophysin-oxytocin complex, the X-ray structures of unbound oxytocin analogues and the NMR-derived structure for bound oxytocin. We find that while our structure is in agreement with the previous crystallographic findings, it differs from the NMR result with regard to how Tyr 2 of the hormone is recognized by neurophysin.
Amino Acid Sequence↗
The evaluation of a new 7-day gonadotropin-releasing hormone agonist protocol in the controlled ovarian hyperstimulation for in vitro fertilization.
OBJECTIVE: Gonadotropin-releasing hormone agonist (GnRHa) was used in the controlled ovarian hyperstimulation (COH) for the in vitro fertilization program. However, the traditional long protocol demanded more human menopause gonadotropin (hMG) and sometimes causes unnecessary delay in the procedure. A new 7-day GnRHa/hMG protocol required to conserve cost and time is thus evaluated for better outcome. METHODS: Sixty consecutive IVF candidates less than 40 years of age were recruited for the study. Cases with severe male factor or polycystic ovarian disease were excluded. The perspective candidates were divided into two groups, one received the traditional, GnRHa2hMG protocol and the other received the new 7-day regimen. RESULTS: When comparing the results in pregnancy rate (33.3% vs 30%), cleavage rate (75.7% vs 75.5%), and the number of oocyte obtained (5.96 +/- 0.91 vs 6.63 +/- 0.90), the 7-day GnRHa/hMG protocol is as good as those of the traditional regimen. The amount of hMG used nevertheless was significantly less (21.48 +/- 0.78 vs 50.59 +/- 2.07). CONCLUSIONS: The new regimen will surely reduce the cost to relieve patient's financial burden and to increase patient's comfort.
Adult↗
Changes in phases and crystallinity of plasma-sprayed hydroxyapatite coatings under heat treatment: a quantitative study.
With three kinds of plasma-sprayed hydroxyapatite coatings (HACs) prepared, the objectives of this study were (1) to establish the calibration methods for quantitatively measuring the concentration of impurity phases and the degree of crystallinity of the HACs, and (2) to explore the effects of postheat treatments at various temperatures in vacuo on the changes of phases and crystallinity of the HACs. By the internal standard method used, the concentrations of impurity phases, such as alpha-TCP, beta-TCP, and TP, of the assprayed HACs were significantly higher than those measured by the direct intensity-ratio method, and the CaO phase was lower than the direct intensity-ratio method. When the HACs were heat treated in the temperature interval 630-850 degrees C, the concentrations of impurity phases obviously decreased, and the coating crystallinity apparently increased. After annealing at 850 degrees C, an HAC consisting of at least 95% crystallinity with few impurity phases was obtained. As the annealing temperatures in the interval 850-1000 degrees C were applied, however, the HA phase seriously decomposed, resulting in the appearance of a large number (higher than 20 wt%) of impurity phases in the HACs. This work suggests that the optimum heat treatment conditions in vacuo for maximizing crystallinity and minimizing impurity phases of the HACs do not occur at the same temperature.
Alloys↗
Progress toward the tertiary structure of (class 3) aldehyde dehydrogenase.
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Aldehyde Dehydrogenase↗
The antinociceptive effect of S-(+)-ibuprofen in rabbits: epidural versus intravenous administration.
This study was designed to determine whether systemic absorption plays any role in the antinociceptive effect of epidural (EP) sodium S(+)-ibuprofen (IB). One week after surgical implantation of EP catheters, six rabbits were given EP injections with either normal saline (NS) 0.4 mL or IB 10 mg in 0.4 mL NS (Group 1) on separate days. Each animal was injected with IB 10 mg intravenously (i.v.) on another day. Six control rabbits (Group 2) had neither surgery nor any injection. Analgesic testing was performed using electric stimulation through two electrocardiogram (ECG) skin electrodes with built-in adhesive, attached to shaved hip areas using 50 V, 1 Hz, 3 ms, before and 0.5,1,2 and 3 h after injection in Group 1, and in similar times in controls. The 95% confidence intervals (CI) of the mean difference between baseline and maximal nociceptive response latency of all groups were compared using analysis of covariance (ANCOVA) adjusted for baseline measurements. This comparison covered all possible pairs among all groups. Significant antinociceptive effects were seen after EP IB but not after control or i.v. IB. Neither motor dysfunction nor evidence of systemic toxicity or neurotoxicity was observed in any animal.
Analgesics↗
Comparison of human menopausal gonadotropin and follicle-stimulating hormone with gonadotropin-releasing hormone agonist desensitization for controlled ovarian hyperstimulation in in vitro fertilization.
BACKGROUND: A pregnancy in patients treated with gonadotropin-releasing hormone agonists (GnRHa) using follicle-stimulating hormone (FSH) alone was first reported by Shaw et al. in 1991. Recently, several comparative trials have shown that FSH is as effective as human menopausal gonadotropin (hMG) in this indication. In other words, the residual endogenous levels of luteinizing hormone (LH) in GnRHa treated cycles may be generally sufficient to support FSH-induced follicular development to exempt from the co-administration of exogenous LH. METHODS: A total of 42 consecutive candidates for in vitro fertilization (IVF) participated in a prospective randomized study. In this study, the efficacy of two different gonadotropins (Pergonal and Metrodin, Serono, Italy) in inducing ovulation was investigated. All treated women were less than 40 years of age and had received a long desensitized protocol by a GnRHa (Leuprolide acetate, Takeda or Decapeptyl, Ferring). Ovarian inactivity was monitored by plasma estradiol and LH concentration. After the pituitary gland was down-regulated, all patients were given either hMG (n = 25) or FSH (n = 17) for controlled ovarian hyperstimulation (COH). RESULTS: The mean number of gonadotropin ampoules and the peak estradiol level were significantly higher in hMG group than in the FSH group. No significant differences were found between both groups in the incidence of cancelled cycles, failed oocyte recovery, mean number of oocytes recovered per patient, the fertilization and embryo cleavage-rate. However, the hMG group demonstrated a higher pregnancy and abortion rate. CONCLUSIONS: There is no significant difference between hMG and FSH stimulation when used following GnRHa desensitization for COH, so the cost should be considered.
Adult↗
The thumb's knuckle. Flexibility in the thumb subdomain of T7 RNA polymerase is revealed by the structure of a chimeric T7/T3 RNA polymerase.
We have solved the structure of a chimeric T7/T3 RNA polymerase (RNAP) in an orthorhombic crystal by molecular replacement with the T7 RNAP structure determined from a monoclinic crystal. The structure of the protruding "thumb" subdomain of the polymerase appears very different in these two crystals apparently because of differences in packing contacts made by the thumb subdomain. These observations support the proposal that the thumb subdomain is flexible and can wrap around bound template to obstruct polymerase: template dissociation during processive synthesis.
Amino Acid Sequence↗
Crystals of glutamine-binding protein in various conformational states.
Crystals of glutamine-binding protein (GlnBP) in various conformational states have been obtained. Crystals of the ligand-free "open" state (denoted form B) have unit cell dimensions a = 86.3 A, b = 86.3 A, c = 81.5 A, alpha = beta = gamma = 90 degrees and diffract to about 2.3 A resolution. An analysis of the intensity data using an Requiv plot indicates that the crystal system is orthorhombic, space group P2(1)2(1)2(1). Crystals of the ligand-bound "open" state (form B*) are obtained by soaking form B crystals with glutamine (Gln) and diffract to about 1.9 A. Crystals of the GlnBP-Gln complex in a ligand-bound "closed" state (form C) belong to space group P2(1)2(1)2(1) with a = 62.0 A, b = 65.7 A and c = 121.8 A and diffract to about 2.3 A. Crystals of a selenomethionyl GlnBP (form B') are isomorphous to form B crystals and diffract to about 2.1 A resolution.
Carrier Proteins↗
Improved crystals of the toxic protein MAP by protein engineering towards the host specificity.
Mirabilis anti-viral protein (MAP) is a ribosome-inactivating protein from Mirabilis jalapa L. Since MAP is effective over a broad spectrum of species, the protein is difficult to express in heterologous hosts such as Escherichia coli. Recently, we obtained a MAP mutant, Y72F which exhibits a lower (1/100) activity against E. coli ribosomes while retaining almost full activity against mammalian cells [Habuka, Miyano, Kataoka, Tsuge & Noma (1992). J. Biol. Chem. 267, 7758-7760]. For the crystallographic studies, the Y72F MAP expression vector with an OmpA leading sequence was constructed and expressed in E. coli. The Y72F MAP mutant was then isolated and purified from the cell culture medium. Crystals were grown using the crystallization conditions for the native MAP crystals [Miyano et al. (1992). J. Mol. Biol. 226, 281-283]: 50% ammonium sulfate containing 50 mM ammonium citrate and 2 mM adenine sulfate, pH 5.4. The crystals belong to space group P3(1)21 (or P3(2)21) with a = b = 104.1 and c = 134.3 A. The crystals are isomorphous with the wild-type crystals but diffract to higher resolution. Imaging-plate photographs of the Y72F mutant showed sharp intense spots without the streaking observed in the native crystals.
Journal Article↗
New crystal forms of a micro-class glutathione S-transferase from rat liver.
Two new crystal forms of isoenzyme 3-3 of rat liver glutathione S-transferase (GST 3-3) have been obtained. They were grown under essentially the same crystallization conditions as those reported for the C2 crystal form [Fu, Rose, Chung, Tam & Wang (1991). Acta Cryst. B47, 813-814]. The new crystals belong to space group P2(1) with one form having cell dimensions a = 101.6, b = 69.5, c = 81.4 A, and beta = 113.6 degrees, and the other form having cell parameters a = 97.4, b = 81.1, c = 69.4 A and beta = 109.2 degrees. These new crystals diffract to at least 2.5 A, resolution. The molecular packing arrangements in these P2(1) crystals have been found by molecular replacement studies.
Journal Article↗
The octameric histone core of the nucleosome. Structural issues resolved.
The crystal structure of the histone octamer has now been determined at 3.1 A resolution and refined to a crystallographic R value of 25.5%. The overall shape of the structure is significantly different from that originally reported by Burlingame et al. and its length is now in agreement with that observed by Klug et al. in their low-resolution studies. The experimental intensity data used in constructing the new electron density map were the same as those used by Burlingame et al. for the original electron density map. In addition, the methods used in producing the new density map were also the same as those for the original map. The only difference between the two calculations was the selection of the heavy-atom location. The large change seen in the structural image (110 A x 70 A x 70 A versus 55 A x 70 A x 70 A) was due to a relatively small change (2.27 A shift) of the heavy-atom site. The fact that the shape and size of the original structure were incorrect is surprising and unusual, since the electron density map that produced the original model was clear for most parts of the structure; one could easily see the well-formed right-handed helices of the H2A and H2B molecules, and the ordered parts of the H2A and H2B molecules could be easily traced from end to end. A comparison of the two maps shows that the original image was derived from two fused copies of the correct structure rotated by +/- 120 degrees from its true location along a rotation axis parallel to the z-axis and the image seen was a partial (about 19.5%) overlap of two molecules. An explanation is given as to how such a small shift of the heavy-atom position could create such a double image in the unit cell, and how the original electron density map could be converted to the new map by a phase modification in the Fourier synthesis. This study resolves the differences between the analyses of the shape and size of the histone octamer structure.
Crystallography, X-Ray↗