Byeong-Gu Han
Sungkyunkwan University
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Publication
Featured researches published by Byeong-Gu Han.
Multiple Sclerosis Journal | 2012
Woojun Kim; Ji Eun Lee; Xue Feng Li; Su-Hyun Kim; Byeong-Gu Han; Byung Il Lee; Jong Kuk Kim; Kyungho Choi; Ho Jin Kim
Background: Antibodies to aquaporin-4 (AQP4-Ab), known as NMO-IgG, are a sensitive and specific marker for neuromyelitis optica (NMO). Methods: To develop an enzyme-linked immunosorbent assay (ELISA) for AQP4-Ab, we expressed M23 isoform of human AQP4 in a baculovirus system, and used it as an antigen. We measured AQP4-Ab in the sera of 300 individuals: 64 with definite NMO, 31 with high-risk NMO, 105 with multiple sclerosis (MS), 57 with other neurological diseases (ONDs), and 43 healthy controls. We also performed longitudinal measurements of AQP4–Ab in 787 samples collected from 51 patients with definite or high-risk NMO. Results: AQP4-Abs were positive in 72% with definite NMO, 55% with high-risk NMO, and 4% with MS, but none of the OND patients and the healthy individuals. The longitudinal measurement showed AQP4-Ab levels correlating with disease activity. Out of 38 initially seropositive patients, 21 became seronegative under effective immunosuppressive therapy. During most relapses, the serum AQP4-Ab levels were either high or rising compared with the previous value, although rising AQP4-Ab levels did not always lead to acute exacerbation. Two of the 13 initially seronegative patients converted to seropositive following acute exacerbations. Conclusions: We established an AQP4-Ab ELISA, which could be a potential monitoring tool of disease activity.
International Journal of Biological Macromolecules | 2010
Byeong-Gu Han; Jea-Won Cho; Young Doo Cho; Kyung-Chae Jeong; Soo-Youl Kim; Byung Il Lee
Transglutaminase 2 (TG2) is a calcium-dependent multifunctional protein associated with various human diseases. We determined the crystal structure of human TG2 in complex with adenosine triphosphate (ATP). The ATP molecule binds to the previously identified guanosine diphosphate (GDP) binding pocket but has different hydrogen bonds and ion interaction with protein. The four residues Arg476, Arg478, Val479 and Tyr583, all of which are involved in both ATP and GDP binding by hydrogen bonds, might play important roles in the stabilization of TG2 by ATP or GDP. However, Ser482 and Arg580, which are involved in GDP binding, do not form hydrogen bond with ATP. Additionally, we newly discovered an intramolecular disulfide bond between Cys230 and Cys370, which formation might regulate the enzymatic activity of TG2.
Proceedings of the National Academy of Sciences of the United States of America | 2010
Do Jin Kim; Kang-Seo Park; Jung Ho Kim; Sang-Hwa Yang; Ji Young Yoon; Byeong-Gu Han; Hyoun Sook Kim; Sang Jae Lee; Jun Young Jang; Kyoung Hoon Kim; Mi Jung Kim; Jin-Su Song; Hie-Joon Kim; Chung-Mo Park; Sang-Kyou Lee; Byung Il Lee; Se Won Suh
There has been considerable interest in virulence genes in the plasticity region of Helicobacter pylori, but little is known about many of these genes. JHP940, one of the virulence factors encoded by the plasticity region of H. pylori strain J99, is a proinflammatory protein that induces tumor necrosis factor-alpha and interleukin-8 secretion as well as enhanced translocation of NF-κB in cultured macrophages. Here we have characterized the structure and function of JHP940 to provide the framework for better understanding its role in inflammation by H. pylori. Our work demonstrates that JHP940 is the first example of a eukaryotic-type Ser/Thr kinase from H. pylori. We show that JHP940 is catalytically active as a protein kinase and translocates into cultured human cells. Furthermore, the kinase activity is indispensable for indirectly up-regulating phosphorylation of NF-κB p65 at Ser276. Our results, taken together, contribute significantly to understanding the molecular basis of the role of JHP940 in inflammation and subsequent pathogenesis caused by H. pylori. We propose to rename the jhp940 gene as ctkA (cell translocating kinase A).
Cancer Letters | 2009
Kang-Seo Park; Byeong-Gu Han; Kyoung Hwa Lee; Dae-Seok Kim; Jung-Mo Kim; Hyesung Jeon; Hyoun Sook Kim; Se Won Suh; Eunjoo H. Lee; S. Kim; Byung Il Lee
It has been suggested that nucleophosmin has an anti-apoptotic function via Bax binding. We found that nucleophosmin is a substrate of transglutaminase 2 (TGase 2) in cancer cells. Increased expression of TGase 2 expression is highly associated with drug resistance, and polymerization of nucleophosmin by TGase 2 also can be correlated with the drug resistance of cancer cells. In the present study, an accumulation of nucleophosmin in cytosol was detected when doxorubicin was treated to cancer cells, and it was found, moreover, that an increase of cytosolic nucleophosmin can result in drug-induced apoptosis. Nucleophosmin was polymerized by TGase 2, and the polymerization was inhibited with the TGase 2 inhibitor, cystamine, in vitro. The nucleophosmin level in the cytosolic cell fraction was reduced when TGase 2 was expressed, and the reduced nucleophosmin level was rescued by cystamine treatment. Moreover, nucleophosmin cross-linked by TGase 2 was eradicated in MCF7 cells via the ubiquitin-proteasomal pathway. In parallel with this nucleophosmin-level restoration, the pro-apoptotic Bax protein level was increased. Therefore, depletion of cytosolic nucleophosmin by TGase 2 can decrease Bax protein stability and lead to anti-apoptosis. Drug-resistant cancer cells became sensitive to doxorubicin treatment when nucleophosmin was expressed in cytosol. Taking these results together, it can be concluded that TGase 2 inhibits accumulation of cytosolic nucleophosmin through polymerization, which results in drug resistance in cancer cells.
Biochemical and Biophysical Research Communications | 2010
Dae-Seok Kim; Byeong-Gu Han; Kang-Seo Park; Byung Il Lee; Soo-Youl Kim; Chang-Dae Bae
Transglutaminase 2 (TGase2) is a calcium-dependent, cross-linking enzyme that catalyzes iso-peptide bond formation between peptide-bound lysine and glutamine residues. TGase 2 can activate NF-kappaB through the polymerization-mediated depletion of I-kappaBalpha without IKK activation. This NF-kappaB activation mechanism is associated with drug resistance in cancer cells. However, the polymers cannot be detected in cells, while TGase 2 over-expression depletes free I-kappaBalpha, which raises the question of how the polymerized I-kappaBalpha can be metabolized in cells. Among proteasome, lysosome and calpain systems, calpain inhibition was found to effectively increase the accumulation of I-kappaBalpha polymers in MCF7 cells transfected with TGase 2, and induced high levels of I-kappaBalpha polymers as well in MDA-MB-231 breast cancer cells that naturally express a high level of TGase 2. Inhibition of calpain also boosted the level of I-kappaBalpha polymers in HEK-293 cells in case of TGase 2 transfection either with I-kappaBalpha or I-kappaBalpha mutant (S32A, S36A). Interestingly, the combined inhibition of calpain and the proteasome resulted in an increased accumulation of both I-kappaBalpha polymers and I-kappaBalpha, concurrent with an inhibition of NF-kappaB activity in MDA-MB-231 cells. This suggests that mu-calpain proteasome-dependent I-kappaBalpha polymer degradation may contribute to cancer progression through constitutive NF-kappaB activation.
FEBS Journal | 2016
Sang Jae Lee; Jang-Sik Choi; Byeong-Gu Han; Hyoun Sook Kim; Ho-Juhn Song; Jaekyoo Lee; Seungyoon Nam; Sung-Ho Goh; Jung Ho Kim; Jong Sung Koh; Byung Il Lee
Spleen tyrosine kinase (SYK) is a cytosolic nonreceptor protein tyrosine kinase that mediates key signal transduction pathways following the activation of immune cell receptors. SYK regulates cellular events induced by the B‐cell receptor and Fc receptors with high intrinsic activity. Furthermore, SYK has been regarded as an attractive target for the treatment of autoimmune diseases and cancers. Here, we report the crystal structures of SYK in complex with seven newly developed inhibitors (G206, G207, O178, O194, O259, O272, and O282) to provide structural insights into which substituents of the inhibitors and binding regions of SYK are essential for lead compound optimization. Our kinase inhibitors exhibited high inhibitory activities against SYK, with half‐maximal inhibitory concentrations (IC50) of approximately 0.7–33 nm, but they showed dissimilar inhibitory activities against KDR, RET, JAK2, JAK3, and FLT3. Among the seven SYK inhibitors, O272 and O282 exhibited highly specific inhibitions against SYK, whereas O194 exhibited strong inhibition of both SYK and FLT3. Three inhibitors (G206, G207, and O178) more efficiently inhibited FLT3 while still substantially inhibiting SYK activity. The binding mode analysis suggested that a highly selective SYK inhibitor can be developed by optimizing the functional groups that facilitate direct interactions with Asn499.
PLOS ONE | 2013
Sang Jae Lee; Byeong-Gu Han; Jea-Won Cho; Jang-Sik Choi; Jaekyoo Lee; Ho-Juhn Song; Jong Sung Koh; Byung Il Lee
Human Pim1 kinase is a serine/threonine protein kinase that plays important biological roles in cell survival, apoptosis, proliferation, and differentiation. Moreover, Pim1 is up-regulated in various hematopoietic malignancies and solid tumors. Thus, Pim1 is an attractive target for cancer therapeutics, and there has been growing interest in developing small molecule inhibitors for Pim1. Here, we describe the crystal structure of Pim1 in complex with a newly developed pyrido[4,3-d]pyrimidine-derivative inhibitor (SKI-O-068). Our inhibitor exhibits a half maximum inhibitory concentration (IC50) of 123 (±14) nM and has an unusual binding mode in complex with Pim1 kinase. The interactions between SKI-O-068 and the Pim1 active site pocket residue are different from those of other scaffold inhibitor-bound structures. The binding mode analysis suggests that the SKI-O-068 inhibitor can be improved by introducing functional groups that facilitate direct interaction with Lys67, which aid in the design of an optimized inhibitor.
Acta Crystallographica Section F-structural Biology and Crystallization Communications | 2013
Jea-Won Cho; Byeong-Gu Han; Sang Youn Park; Seung Jun Kim; Myoung-Dong Kim; Byung Il Lee
Bacteroides thetaiotaomicron BT0793, a putative xylose isomerase, was overexpressed in Escherichia coli, purified and crystallized using polyethylene glycol monomethyl ether 550 as the precipitant. X-ray diffraction data were collected to 2.10 Å resolution at 100 K using synchrotron X-rays. The crystal was found to belong to space group P1, with unit-cell parameters a=96.3, b=101.7, c=108.3 Å, α=82.8, β=68.2, γ=83.0°. The asymmetric unit contained eight subunits of xylose isomerase with a crystal volume per protein weight (VM) of 2.38 Å3 Da(-1) and a solvent content of 48.3%.
Acta Crystallographica Section F-structural Biology and Crystallization Communications | 2011
Byeong-Gu Han; Byung Il Lee
Pyrococcus furiosus PF2050, a putative uncharacterized protein, was overexpressed in Escherichia coli, purified and crystallized at 298 K using 2-methyl-2,4-pentanediol as the precipitant. X-ray diffraction data were collected to a resolution of 1.56 Å at 100 K using synchrotron X-rays. The crystal was found to belong to space group P2(1), with unit-cell parameters a = 41.76, b = 66.43, c = 46.38 Å, β = 96.62°. The asymmetric unit contained one subunit of PF2050, with a crystal volume per protein weight (V(M)) of 2.21 Å(3) Da(-1) and a solvent content of 44.41%.
Journal of Molecular Biology | 2009
Jun Young Jang; Hye-Jin Yoon; Ji Young Yoon; Hyoun Sook Kim; Sang Jae Lee; Kyoung Hoon Kim; Do Jin Kim; Soonmin Jang; Byeong-Gu Han; Byung Il Lee; Se Won Suh