A5064016950- Nuclear Structure and Function
- RNA Research and Splicing
- DNA Repair Mechanisms
- Bacterial Genetics and Biotechnology
- Genomics and Chromatin Dynamics
- Enzyme Structure and Function
- Skin and Cellular Biology Research
- Vibrio bacteria research studies
- Escherichia coli research studies
- Redox biology and oxidative stress
- Cancer Genomics and Diagnostics
- Glycosylation and Glycoproteins Research
- Sulfur Compounds in Biology
- Renal cell carcinoma treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Alzheimer's disease research and treatments
- Cholinesterase and Neurodegenerative Diseases
- Amyotrophic Lateral Sclerosis Research
- Enzyme Production and Characterization
- Amino Acid Enzymes and Metabolism
- Cancer Research and Treatments
- Folate and B Vitamins Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Water Treatment and Disinfection
- Legionella and Acanthamoeba research
Seoul National University
2015-2023
Institute for Basic Science
2023
Yonsei University
2012
Asan Medical Center
2012
Abstract Nuclear structure and function are governed by lamins, which intermediate filaments that mostly consist of α-helices. Different lamin assembly models have been proposed based on low resolution fragmented structures. However, their mechanisms still poorly understood at the molecular level. Here, we present crystal a long human fragment 3.2 Å allows visualization features full-length protein. The shows an anti-parallel arrangement two coiled-coil dimers, is important for process. We...
Abstract Previous work has revealed that progerin-lamin A binding inhibitor (JH4) can ameliorate pathological features of Hutchinson-Gilford progeria syndrome (HGPS) such as nuclear deformation, growth suppression in patient’s cells, and very short life span an vivo mouse model. Despite its favorable effects, JH4 is rapidly eliminated pharmacokinetic (PK) analysis. Thus, we improved property through chemical modification obtained optimized drug candidate, Progerinin (SLC-D011). This extend...
Neurodegenerative diseases such as Parkinson's disease (PD) are known to be related oxidative stress and neuroinflammation, thus, modulating neuroinflammation offers a possible means of treating PD-associated pathologies. Morin (2',3,4',5,7-pentahydroxy flavone) is flavonol with anti-oxidative anti-inflammatory effects found in wines, herbs, fruits. The present study was undertaken determine whether morin-containing diet has protective an MPTP-induced mouse model PD. Mice were fed control or...
Hypochlorous acid (HOCl) is generated in the immune system to kill microorganisms. In Escherichia coli , a hypochlorite-specific transcription regulator, HypT, has been characterized. HypT belongs LysR-type transcriptional regulator (LTTR) family that contains DNA-binding domain (DBD) and regulatory (RD). Here, we identified hypT gene from Salmonella enterica serovar Typhimurium determined crystal structures of full-length protein RD. The structure reveals type tetrameric assembly LTTR...
In response to microbial invasion, the animal immune system generates hypochlorous acid (HOCl) that kills microorganisms in oxidative burst. HOCl toxicity is amplified phagosome through import of copper cation (Cu2+). Escherichia coli and Salmonella, transcriptional regulator RclR senses stress induces expression RclA, -B, -C proteins involved bacterial defenses against stress. However, structures biochemical roles Rcl remain be elucidated. this study, we first examined role flavoprotein...
Abstract Eukaryotic Cu, Zn-superoxide dismutase (SOD1) is primarily responsible for cytotoxic filament formation in amyotrophic lateral sclerosis (ALS) neurons. Two cysteine residues SOD1 form an intramolecular disulfide bond. This study aims to explore the molecular mechanism of by overoxidation sporadic ALS (sALS). In this study, we determined crystal structure double mutant (C57D/C146D) that mimics disulfide-forming residues. The revealed open and relaxed conformation loop IV containing...
Nuclear lamins maintain the nuclear envelope structure by forming long linear filaments via two alternating molecular arrangements of coiled-coil dimers, known as A11 and A22 binding modes. The mode is characterized antiparallel interactions between coil 1b domains, whereas facilitated 2 domains lamin. junction A11- A22-interacting dimers in lamin tetramer produces another parallel head-tail interaction 1a C-terminal region 2, called ACN interaction. During mitosis, phosphorylation...
Abstract Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective death of motor neurons. Mutations in Cu, Zn-superoxide dismutase (SOD1) causing the gain its toxic property are major culprit familial ALS (fALS). The abnormal SOD1 aggregation neurons has been suggested as pathological hallmark patients. However, development pharmacological interventions against still needs further investigation. In this study, using ELISA-based chemical screening...
Intermediate filaments (IFs) commonly have structural elements of a central α-helical coiled-coil domain consisting coil 1a, 1b, 2, and their flanking linkers. Recently, the crystal structure long lamin A/C fragment was determined showed detailed features tetrameric unit. The further suggested new binding mode between tetramers, designated eA22, where parallel overlap 1a 2 is critical interaction. This study investigated biochemical effects genetic mutations causing human diseases, focusing...
Most Gram-negative bacteria respond to excessive levels of H2O2 using the peroxide-sensing transcriptional regulator OxyR, which can induce expression antioxidant genes restore normality. Vibrio vulnificus has two distinct OxyRs (OxyR1 and OxyR2), are sensitive different peroxidases, Prx1 Prx2. Although OxyR1 both high sequence similarity sensitivity comparable with that other OxyR proteins, OxyR2 exhibits limited is more To investigate basis for this difference, we determined crystal...
The Gram-negative opportunistic pathogen, Pseudomonas aeruginosa , has multiple multidrug efflux pumps. MexT, a LysR-type transcriptional regulator, functions as activator of the MexEF-OprN system. MexT consists an N-terminal DNA-binding domain and C-terminal regulatory (RD). Little is known regarding ligands its mechanism activation. We elucidated crystal structure RD at 2.0 Å resolution. comprised two protomer chains in dimeric arrangement. possessed arginine-rich region hydrophobic patch...
Many enzymes require pyridoxal 5’-phosphate (PLP) as an essential cofactor and share active site residues in mediating diverse enzymatic reactions. Methionine can be converted into cysteine by cystathionine γ-lyases (CGLs) through a transsulfuration reaction dependent on PLP. In bacteria, MccB, also known YhrB, exhibits CGL activity that cleaves the C–S bond of at γ position. this study, we determined crystal structure MccB from Staphylococcus aureus its apo- PLP-bound forms. The structures...
The nucleoskeletal protein lamin is primarily responsible for the mechanical stability of nucleus.The assembly process requires A11, A22, and ACN binding modes coiled-coil dimers.Although X-ray crystallography chemical cross-linking analysis A/C have provided snapshots A11 modes, mechanism entire filament remains to be explained.Here, we report a crystal structure coil 2 fragment, revealing A22 interaction at atomic resolution.The showed detailed structural features, indicating that two...
LysR-type transcriptional regulators (LTTRs) contain an N-terminal DNA binding domain (DBD) and a C-terminal regulatory (RD). Typically, LTTRs function as homotetramers. VV2_1132 was identified in
Abstract Werner syndrome (WRN) is a rare progressive genetic disorder, caused by functional defects in WRN protein and RecQ4L DNA helicase. Acceleration of the aging process initiated at puberty expected life span approximately late 50 s. However, Wrn -deficient mouse model does not show premature phenotypes or short span, implying that processes differ greatly between humans mice. Gene expression analysis cells reveals very similar results to gene Hutchinson Gilford progeria (HGPS) cells,...
Proposed is a novel miniaturisation method of coaxial beam-rotating antenna (COBRA) lens horn for high power application. Generally, miniaturised increases the phase error at aperture because large flare angle which causes gain decrease. However, since proposed COBRA compensates with modified lens, radiation characteristics such as and pattern are similar to conventional one while length reduced by more than 50%.
Lamins are intermediate filaments that form a 3-D meshwork in the periphery of nuclear envelope. The recent crystal structure long fragment human lamin A/C visualized tetrameric assembly unit central rod domain as polymerization intermediate. A genetic mutation S143F caused phenotype characterized by both progeria and muscular dystrophy. In this study, we determined harboring mutation. obtained revealed X-shaped interaction between units crystals, potentiated hydrophobic interactions mutated...
Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidase enzymes. Recently, a new type of Prx, Vv Prx3, was identified in the pathogenic bacterium Vibrio vulnificus as being important for survival macrophages. It employs only one catalytic cysteine residue to decompose peroxides. Here, crystal structures Prx3 representing its reduced and oxidized states have been determined, together with an H 2 O -bound structure, at high resolution. The structure showed typical dimeric interface,...
Cryo-electron microscopy (cryo-EM) is now the first choice to determine high-resolution structures of huge protein complexes. Grids with two-dimensional arrays holes covered a carbon film are typically used in cryo-EM. Although semi-automatic plungers available, notable trial-and-error still required obtain suitable grid specimen. Herein, we introduce new method thin ice specimens using real-time measurement liquid amounts cryo-EM grids. The grids for strongly diffracted laser light, and...
A recent genetic study with Brucella abortus revealed the secretion activator gene (SagA) as an autolysin component creating pores in peptidoglycan (PGN) layer for type IV system (T4SS) and hydrolase inhibitor (PhiA) of SagA.In this study, we determined crystal structures both SagA PhiA.Notably, structure contained a PGN fragment space between N-and C-terminal domains, showing substrate-dependent hinge motion domains.The purified fully hydrolyzed meso-diaminopimelic acid (DAP)-type PGN,...