A5101556935- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Cholesterol and Lipid Metabolism
- Cancer-related gene regulation
- Nuclear Structure and Function
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Lipid metabolism and biosynthesis
- Fungal and yeast genetics research
- Chromosomal and Genetic Variations
- Heme Oxygenase-1 and Carbon Monoxide
- Steroid Chemistry and Biochemistry
- Cancer, Lipids, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Folate and B Vitamins Research
- Plant biochemistry and biosynthesis
- Plant-derived Lignans Synthesis and Bioactivity
- Porphyrin Metabolism and Disorders
- Metal-Catalyzed Oxygenation Mechanisms
- Genomics, phytochemicals, and oxidative stress
- Microbial metabolism and enzyme function
- Histone Deacetylase Inhibitors Research
- Phytochemical Studies and Bioactivities
- DNA Repair Mechanisms
University of Michigan–Ann Arbor
2015-2025
Korea Advanced Institute of Science and Technology
2011-2020
Michigan United
2017
Korea Research Institute of Bioscience and Biotechnology
2003-2010
Yonsei University
2006-2008
Abstract Sestrins are stress-inducible metabolic regulators with two seemingly unrelated but physiologically important functions: reduction of reactive oxygen species (ROS) and inhibition the mechanistic target rapamycin complex 1 (mTORC1). How fulfil this dual role has remained elusive so far. Here we report crystal structure human Sestrin2 (hSesn2), show that hSesn2 is twofold pseudo-symmetric globular subdomains, which structurally similar functionally distinct from each other. While...
Absent, small, or homeotic disc1 (Ash1) is a trithorax group histone methyltransferase that involved in gene activation. Although there are many known methyltransferases, their regulatory mechanisms poorly understood. Here, we present the crystal structure of human ASH1L catalytic domain, showing its substrate binding pocket blocked by loop from post-SET domain. In this configuration, limits access to active site. Mutagenesis stimulates activity, suggesting activity may be regulated through...
Mixed lineage leukemia (MLL) family histone methyltransferases are enzymes that deposit H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals. Despite extensive structural biochemical studies, the molecular mechanisms whereby MLL complexes recognize H3K4 within nucleosome core particles (NCPs) remain unclear. Here we report single-particle cryo-electron microscopy (cryo-EM) structure of NCP-bound human MLL1 complex. We show complex anchors to NCP via conserved RbBP5...
Following recent advancements in cryo-electron microscopy (cryo-EM) instrumentation and software algorithms, the next bottleneck achieving high-resolution cryo-EM structures arises from sample preparation. To overcome this, we developed a graphene-based affinity grid, Graffendor (GFD) to target low-abundance endogenous protein complexes. maintain grid quality consistency within single batch of 36 grids, established one-step crosslinking batch-production method using genetically modified ALFA...
Soluble methane monooxygenase in methanotrophs converts to methanol under ambient conditions. The maximum catalytic activity of hydroxylase (MMOH) is achieved through the interplay its regulatory protein (MMOB) and reductase. An additional auxiliary protein, MMOD, functions as an inhibitor MMOH; however, inhibitory mechanism remains unknown. Here, we report crystal structure MMOH-MMOD complex from
H3K9 methylation (H3K9me) specifies the establishment and maintenance of transcriptionally silent epigenetic states or heterochromatin. The enzymatic erasure histone modifications is widely assumed to be primary mechanism that reverses silencing. Here, we reveal an inversion this paradigm where a putative demethylase Epe1 in fission yeast, has non-enzymatic function opposes heterochromatin assembly. Mutations within catalytic JmjC domain disrupt its interaction with Swi6HP1 suggesting might...
The influence of ethanolic extracts Brassica campestris spp. rapa roots (EBR) on obesity was examined in imprinting control region (ICR) mice fed a high-fat diet (HFD) and 3T3-L1 adipocytes. ICR used were divided into regular diet, HFD, EBR (50 mg/kg/day administered orally), orlistat (10 orally) groups. molecular mechanism the anti-obesity effect investigated adipocytes as well HFD-fed mice. In obese mouse model, both weight gain epididymal fat accumulation highly suppressed by daily oral...
Abstract Inactivation of tumor suppressor Runt-related transcription factor 3 (RUNX3) plays an important role during early tumorigenesis. However, posttranslational modifications (PTM)-based mechanism for the inactivation RUNX3 under hypoxia is still not fully understood. Here, we demonstrate a that G9a, lysine-specific methyltransferase (KMT), modulates through PTM hypoxia. Hypoxia significantly increased G9a protein level and interacted with Runt domain, which led to methylation at K129...
Kap123, a major karyopherin protein of budding yeast, recognizes the nuclear localization signals (NLSs) cytoplasmic histones H3 and H4 translocates them into nucleus during DNA replication. Mechanistic questions include H3- H4-NLS redundancy toward Kap123 role conserved diacetylation (K5ac K12ac) in Kap123-mediated histone translocation. Here, we report crystal structures full-length Kluyveromyces lactis alone complex with H4-NLSs. Structures reveal unique feature that possesses two...
Antiatherosclerotic effects of ethanolic extracts Artemisia princeps Pampanini cv. Sajabal (ESJ) were investigated in low-density lipoprotein receptor deficient (LDLR(-/-)) mice. The Western diet-induced high levels total cholesterol and triglyceride similar the ESJ control groups. However, circulating oxidized LDL was significantly decreased group (p < 0.05). also markedly aortic expression intercellular adhesion molecule-1 (ICAM-1), vascular cell (VCAM-1), tumor necrosis factor-alpha...
We investigated the mechanism of spontaneous cholesterol efflux induced by acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibition, and how an alteration metabolism in macrophages impacts on that HepG2 cells. Oleic acid anilide (OAA), a known ACAT inhibitor reduced lipid storage substantially promotion catabolism repression cholesteryl ester accumulation without further increase cytotoxicity acetylated low-density lipoprotein-loaded THP-1 macrophages. Analysis expressed mRNA protein...
Acyl-CoA: cholesterol acyltransferase (ACAT) plays an important role in the esterification of with its substrates, and fatty acyl coenzyme A, to facilitate both intracellular storage intercellular transport. ACAT-1 is more involved macrophage foam cell formation ACAT-2 a critical absorption process intestinal enterocytes. Three aliphatic acid amides, β-sanshool (1), γ-sanshool (2), hydroxy-β-sanshool (3), were isolated by bioassay-guided fractionation ethanolic extracts Zanthoxylum piperitum...
To investigate a role for histidine residues in the expression of normal acyl‐CoA:cholesterol acyltransferase (ACAT) activity, located at five different positions two isoenzymes were substituted by alanine, based on sequence homology between ACAT1 and ACAT2. Among 10 mutants generated baculovirus technology, H386A–ACAT1, H460A–ACAT1, H360A–ACAT2, H399A–ACAT2 lost their enzymatic activity completely. A reduction catalytic is unlikely to result from structural changes substrate‐binding pocket,...
How cell-type-specific chromatin landscapes emerge and progress during metazoan ontogenesis remains an important question. Transcription factors are expressed in a manner recruit chromatin-regulatory machinery to specific genomic loci. In contrast, proteins broadly assumed exert the same intrinsic function across cell types. However, human genetics studies have revealed unexpected vulnerability of neurodevelopment factor mutations with unknown mechanisms. Here, we report that 14 regulators...
Cobalt–sulfur (Co–S) coordination is labile to both oxidation and reduction chemistry rarely seen in nature. Cobalamin (or vitamin B12) an essential cobalt-containing organometallic cofactor mammals escorted via intricate network of chaperones a single cytoplasmic target, methionine synthase. In this study, we report that the human cobalamin trafficking protein, MMADHC, exploits chemical lability Co–S for off-loading onto Cys-261 on MMADHC serves as β-axial ligand cobalamin. Complex...