Cytosolic peptide:N-glycanase (NGLY1 in mammals), a highly conserved enzyme in eukaryotes, catalyzes the deglycosylation of N-glycans that are attached to glycopeptide/glycoproteins. In 2012, an autosomal recessive disorder related to the NGLY1 gene, which was referred to as NGLY1 deficiency, was reported. Since then, more than 100 patients have been identified. Patients with this disease exhibit various symptoms, including various motor deficits and other neurological problems. Effective therap...
Last. Gota Kawai(Chiba Institute of Technology)H-Index: 23
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Interaction analysis between small molecules and RNA as well as structure determination of RNA-small molecule complexes will be the clues to search for compounds that bind to specific mRNA or non-coding RNA in drug discovery. In this study, the RNA binding ability of a fluoroquinolone derivative, KG022, was examined against single-residue bulge-containing hairpin RNAs as RNA models. NMR analysis indicated that KG022 interacts with the RNAs in the vicinity of the bulge residue, with preferring C ...
Last. Koshi Imami(National Presto Industries)H-Index: 17
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Recent advances in biotinylation-based proximity labeling (PL) have opened up new avenues for mapping the protein composition of cellular compartments and protein complexes in living cells at high spatiotemporal resolution. In particular, PL combined with mass spectrometry-based proteomics has been successfully applied to defining protein-protein interactions, protein-nucleic acid interactions, (membraneless) organelle proteomes, and secretomes in various systems ranging from cultured cells to w...
Many studies of the reconstitution of the Escherichia coli small ribosomal subunit from its individual molecular parts have been reported, but contrastingly, similar studies of the large ribosomal subunit have not been well performed to date. Here, we describe protocols for preparing the 33 ribosomal proteins of the Escherichia coli 50S subunit and demonstrate successful reconstitution of a functionally active 50S particle that can perform protein synthesis in vitro. We also successfully reconst...
Since the discovery of D-Amino acid oxidase (DAO) in 1935, many studies have been conducted without clarifying its three-dimensional structure for a long time. In 1996, the crystal structure of DAO was determined, and it was shown that the catalytic bases required for the two catalytic mechanisms were not present in the active site. The crystal structure of DAO in complex with o-aminobenzoate was solved and is used for modeling Michaelis complex. The Michaelis complex model provided structural i...
#2Seigo Iwata(SUA: Soka University of America)H-Index: 3
Last. Shinsaku Maruta(SUA: Soka University of America)H-Index: 11
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The lipid-anchored small G protein Ras is a central regulator of cellular signal transduction processes, thereby functioning as a molecular switch. Ras forms a nanocluster on the plasma membrane by modifying lipids in the hypervariable region (HVR) at the C-terminus to exhibit physiological functions. In this study, we demonstrated that chemical modification of cysteine residues in HVR with caged compounds (instead of lipidation) induces multimerization of H-Ras. The sulfhydryl-reactive caged co...
Last. Yoshiyuki Horio(Sapporo Medical University)H-Index: 53
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SIRT3 is an NAD+-dependent protein deacetylase localized in mitochondria. Several studies reported localization of SIRT3 in the cytoplasm or nucleus, but data of these studies were not consistent. We detected expression of mitochondrial (SIRT3mt) and cytoplasmic (SIRT3ct) Sirt3 mRNAs in the mouse brain, and we also found SIRT3 immunostaining of mitochondria and cytoplasm in the brain and cultured neural cells. However, expression levels of SIRT3ct in COS cells transfected with SIRT3ct cDNA were ...
I started on crystallographic studies of cytochrome c (Cyt.c) in the later 1960s at Institute for Protein Research, Osaka University. The institute successfully built the structural model of ferro-Cyt.c by the multiple heavy atom replacement method in the early 1970s. In the early 1990s, crystals of cytochrome c oxidase (CcO) from bovine heart were obtained by using polyethylene glycol 4000 (Sigma) as the precipitant. We reported the first structure of a mammalian membrane protein at 2.8 A resol...
Peptide:N-glycanase is an evolutionarily conserved deglycosylating enzyme that catalyzes the removal of N-linked glycans from cytosolic glycoproteins. Recessive mutations that inactivate this enzyme cause NGLY1 deficiency, a multisystemic disorder with symptoms including developmental delay and defects in cognition and motor control. Developing treatments for NGLY1 deficiency will require an understanding of how failure to deglycosylate NGLY1 substrates perturbs cellular and organismal function....
Substrate derived biomarkers are necessary in slowly progressing monogenetic diseases caused by single enzyme deficiencies to identify affected patients and serve as surrogate markers for therapy response. N-glycanase 1 (NGLY1) deficiency is an ultra-rare autosomal recessive disorder characterized by developmental delay, peripheral neuropathy, elevated liver transaminases, hyperkinetic movement disorder, and (hypo)-alacrima. We demonstrate that N-acetylglucosamine-asparagine (GlcNAc-Asn; GNA), i...
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