• Molecules and Cells
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• v.41 no.6
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• pp.545-552
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• 2018

Spleen tyrosine kinase (SYK) is a cytosolic non-receptor protein tyrosine kinase. Because SYK mediates key receptor signaling pathways involving the B cell receptor and Fc receptors, SYK is an attractive target for autoimmune disease and cancer treatments. To date, representative oral SYK inhibitors, including fostamatinib (R406 or R788), entospletinib (GS-9973), cerdulatinib (PRT062070), and TAK-659, have been assessed in clinical trials. Here, we report the crystal structures of SYK in complex with two newly developed inhibitors possessing 4-aminopyrido[4,3-D]pyrimidine moieties (SKI-G-618 and SKI-O-85). One SYK inhibitor (SKI-G-618) exhibited moderate inhibitory activity against SYK, whereas the other inhibitor (SKI-O-85) exhibited a low inhibitory profile against SYK. Binding mode analysis indicates that a highly potent SYK inhibitor might be developed by modifying and optimizing the functional groups that interact with Leu377, Gly378, and Val385 in the G-loop and the nearby region in SYK. In agreement with our structural analysis, one of our SYK inhibitor (SKI-G-618) shows strong inhibitory activities on the ${\beta}$-hexosaminidase release and phosphorylation of SYK/Vav in RBL-2H3 cells. Taken together, our findings have important implications for the design of high affinity SYK inhibitors.

• Molecules and Cells
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• v.42 no.1
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• pp.56-66
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• 2019

Histidine triad nucleotide-binding protein (HINT) is a member of the histidine triad (HIT) superfamily, which has hydrolase activity owing to a histidine triad motif. The HIT superfamily can be divided to five classes with functions in galactose metabolism, DNA repair, and tumor suppression. HINTs are highly conserved from archaea to humans and function as tumor suppressors, translation regulators, and neuropathy inhibitors. Although the structures of HINT proteins from various species have been reported, limited structural information is available for fungal species. Here, to elucidate the structural features and functional diversity of HINTs, we determined the crystal structure of HINT from the pathogenic fungus Candida albicans (CaHINT) in complex with zinc ions at a resolution of $2.5{\AA}$. Based on structural comparisons, the monomer of CaHINT overlaid best with HINT protein from the protozoal species Leishmania major. Additionally, structural comparisons with human HINT revealed an additional helix at the C-terminus of CaHINT. Interestingly, the extended C-terminal helix interacted with the N-terminal loop (${\alpha}1-{\beta}1$) and with the ${\alpha}3$ helix, which appeared to stabilize the dimerization of CaHINT. In the C-terminal region, structural and sequence comparisons showed strong relationships among 19 diverse species from archea to humans, suggesting early separation in the course of evolution. Further studies are required to address the functional significance of variations in the C-terminal region. This structural analysis of CaHINT provided important insights into the molecular aspects of evolution within the HIT superfamily.

• Korean Journal of Microbiology
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• v.55 no.2
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• pp.123-130
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• 2019

Chelatase catalyzes the insertion of divalent metal into tetrapyrrole and plays a key role in the biosynthesis of metallated tetrapyrroles, such as cobalamin, siroheme, heme, and chlorophyll. SirB is a sirohydrochlorin (SHC) chelatase that generates cobalt-SHC or iron-SHC by inserting cobalt or iron into the center of sirohydrochlorin tetrapyrrole. To provide structural insights into the metal-binding and SHC-recognition mechanisms of SirB, we determined the crystal structure of SirB from Bacillus subtilis subsp. spizizenii (bssSirB) in complex with cobalt ions. bssSirB forms a monomeric ${\alpha}/{\beta}$ structure that consists of two domains, an N-terminal domain (NTD) and a C-terminal domain (CTD). The NTD and CTD of bssSirB adopt similar structures with a four-stranded ${\beta}-sheet$ that is decorated by ${\alpha}-helices$. bssSirB presents a highly conserved cavity that is generated between the NTD and CTD and interacts with a cobalt ion on top of the cavity using two histidine residues of the NTD. Moreover, our comparative structural analysis suggests that bssSirB would accommodate an SHC molecule into the interdomain cavity. Based on these structural findings, we propose that the cavity of bssSirB functions as the active site where cobalt insertion into SHC occurs.

• Fibers and Polymers
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• v.3 no.1
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• pp.18-23
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• 2002

The structure development and dynamic properties of fibers produced by high-speed spinning of P(EN-ET) random copolymers were investigated. The as-spun fibers were found to remain amorphous up to the spinning speed of 1500 m/min, and subsequent increases in speed resulted in the crystalline domains containing primarily $\alpha$ crystalline modification of PEN. The f modification was not found up to spinning speeds of 4500 m/min. On the other hand, annealing of constrained fibers spun at the 2100 m/min at 180,200, and 240^{\circ}C$ exhibited $\beta$-form crystalline structure, while the annealed fibers spun in 600-1500 m/min range exhibited dominantly $\alpha$-form. However $\beta$-form crystals disappeared above the spinning speed of 3000 m/min. With increasing spinning speeds from 600 to 4500 m/min, the storage modulus of as-spun fibers increased continuously and reached a value of about 10.4 spa at room temperature. The tan $\delta$curves showed the $\alpha$-relaxation peak at about 155-165^{\circ}C$, which is considered to correspond to the glass transition. The $\alpha$-relaxation peaks became smaller and broader, and shift to higher temperatures as the spinning speed increases, meaning that molecular mobility in the amorphous region is restricted by increased crystalline domain.

• Journal of Advanced Marine Engineering and Technology
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• v.26 no.4
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• pp.439-449
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• 2002

Experimental investigations of the flow structure and heat transfer enhancement in a channel with a built-in circular cylinder and a wing-let type vortex generator are presented. Without any vortex generators, relatively low heat transfer takes place in the downstream of the circular cylinder where is a recirculation region with low velocity fluid is formed. However with a wing-let type longitudinal vortex generator in the wake region behind the cylinder, heat transfer in the region can be enhanced. In order to control the strength of longitudinal vortices, the angle of attack of the vortex generators is varied from $20^{circ} to 45^{\circ}$, but spacings between the vortex generations are fixed to be 5 mm. The 3-dimensional mean velocity field downstream of the vortex generator is measured by a five-hole pressure probe, and the hue-capturing method using thermochromatic liquid crystals has been used to provide the local distribution of the heat transfer coefficient. The vorticity field and streamwise velocity contour are obtained from the velocity field. Streamwise distributions of averaged Stanton number on the measurement planes show very similar trends for all the experimental cases($\beta=20^{circ}, 30^{circ} and 45^{\circ}$). Circulation strength and heat transfer coefficient have the maximum values when the angle of attack($\beta$) is $30^{\circ}$.

• Journal of Sericultural and Entomological Science
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• v.37 no.2
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• pp.127-131
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• 1995

A crude crystal of phytoecdysone was obtained 355 mg per Kg dry radix of A. japonica, and it was identified to $\beta$-ecdysone by TLC. Feeding silkworms on mulberry leaves sprayed with the extract, mounting time shortened and pupation ratio improved. The feeding effects of the extract was differed according to the rearing seasons, spring and summer. In spring season, only mounting time shortened without any difference in pupation ratio from the control. In summer season, not only mounting time shortened, but also pupation ratio remarkably advanced.

• Journal of the Korean Magnetic Resonance Society
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• v.17 no.1
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• pp.59-66
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• 2013

BldD, a developmental transcription factor from Streptomyces coelicolor, is a homodimeric, DNA-binding protein with 167 amino acids in each subunit. Each monomer consists of two structurally distinct domains, the N-terminal domain (BldD-NTD) responsible for DNA-binding and dimerization and the C-terminal domain (BldD-CTD). In contrast to the BldD-NTD, of which crystal structure has been solved, the BldD-CTD has been characterized neither in structure nor in function. Thus, in terms of structural genomics, structural study of the BldD-CTD has been conducted in solution, and in the present work, mainchain NMR assignments of the recombinant BldD-CTD (residues 80-167 of BldD) could be achieved by a series of heteronuclear multidimensional NMR experiments on a [$^{13}C/^{15}N$]-enriched protein sample. Finally, the secondary structure prediction by CSI and TALOS+ analysis using the assigned chemical shifts data identified a ${\beta}-{\alpha}-{\alpha}-{\beta}-{\alpha}-{\alpha}-{\alpha}$ topology of the domain. The results will provide the most fundamental data for more detailed approach to the atomic structure of the BldD-CTD, which would be essential for entire understanding of the molecular function of BldD.

• Journal of the Korean Ceramic Society
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• v.18 no.3
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• pp.187-191
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• 1981

The effect of additions, $TiO_2$ and $ZrO_2$ as nucleant on the base glass which composition was determined to 0.97 $Li_2O-Al_2O_3-SiO_2$ has been investigated by means of D.T.A., X-ray diffraction and dilatation. $TiO_2$ and $ZrO_2$ as nucleant were added 0.06mole, in which ratios of $TiO_2$/$ZrO_2$ were varied 1/0, 2/1, 1/1, 1/2 and 0/1. The crystalline phases were appeared to $\beta$-spodumene as principal, $\beta$-eucryptite and $ZrO_2$ as secondary, regardless of nucleant variations. The crystallinity of the crystallized glass added $TiO_2$, $ZrO_2$ mixture as nucleant was higher than that of the glass added $TiO_2$ or $ZrO_2$ only. The crystallinity of the glass added $TiO_2$/$ZrO_2$ =1/1 was highest. Increasing the addition of $ZrO_2$, it has been observed that the crystal growing temperature became higher.

• Journal of the Korean Chemical Society
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• v.18 no.1
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• pp.25-30
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• 1974

The crystal and molecular structure of monoethanolamine hydrobromide, HOCH2CH2NH2 HBr, has been determined by X-ray diffraction methods. The crystals are triclinic, space group Pi and unit cell contains two formula units and has dimensions a = 4.54, b = 7.45, c = 7.76${\AA}$ and ${\alpha}$ = 102.5, ${\beta}$=93.6, ${\gamma}=78.7^{\circ}$. The present structure determination confirmed that the structure of monoethanolamine hydrobromide is isomorphous with that of monoethanolamine hydrochloride.

• Proceedings of the KIEE Conference
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• 2002.11a
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• pp.106-108
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• 2002

The composites were fabricated 61vol.% $\beta-SiC$ and 39vol.% $TiB_2$ powders with the liquid forming additives of l2wt% $Al_2O_3+Y_2O_3$ by pressureless annealing at $1700^{\circ}C,\;1750^{\circ}C,\;1800^{\circ}C$ for 4 hours respectively. The result of Phase analysis of composites by XRD revealed $\alpha-SiC$(6H), $TiB_2$, and YAG($Al_5Y_3O_{12}$) crystal phase. The relative density and the Young's modulus showed the highest value of 92.9701% and 92.884Gpa for composites by pressureless annealing temperature $1700^{\circ}C$ at room temperature.