Institute of Microbial Chemistry BIKAKEN

Shinagawa-ku, Japan

Institute of Microbial Chemistry BIKAKEN

Shinagawa-ku, Japan

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Noda N.N.,Institute of Microbial Chemistry BIKAKEN | Noda N.N.,Japan Science and Technology Agency | Inagaki F.,Japan Science and Technology Agency | Inagaki F.,Hokkaido University
Annual Review of Biophysics | Year: 2015

The formation of the autophagosome, a landmark event in autophagy, is accomplished by the concerted actions of Atg proteins. The initial step of starvation-induced autophagy in yeast is the assembly of the Atg1 complex, which, with the help of other Atg groups, recruits Atg conjugation systems and initiates the formation of the autophagosome. In this review, we describe from a structural-biological point of view the structure, interaction, and molecular roles of Atg proteins, especially those in the Atg1 complex and in the Atg conjugation systems. © Copyright ©2015 by Annual Reviews. All rights reserved.


Suzuki H.,Institute of Microbial Chemistry BIKAKEN | Kaizuka T.,University of Tokyo | Mizushima N.,University of Tokyo | Noda N.N.,Institute of Microbial Chemistry BIKAKEN | Noda N.N.,Japan Science and Technology Agency
Nature Structural and Molecular Biology | Year: 2015

Atg101 is an essential component of the autophagy-initiating ULK complex in higher eukaryotes, but it is absent from the functionally equivalent Atg1 complex in budding yeast. Here, we report the crystal structure of the fission yeast Atg101-Atg13 complex. Atg101 has a Hop1, Rev7 and Mad2 (HORMA) architecture similar to that of Atg13. Mad2 HORMA has two distinct conformations (O-Mad2 and C-Mad2), and, intriguingly, Atg101 resembles O-Mad2 rather than the C-Mad2-like Atg13. Atg13 HORMA from higher eukaryotes possesses an inherently unstable fold, which is stabilized by Atg101 via interactions analogous to those between O-Mad2 and C-Mad2. Mutational studies revealed that Atg101 is responsible for recruiting downstream factors to the autophagosome-formation site in mammals via a newly identified WF finger. These data define the molecular functions of Atg101, providing a basis for elucidating the molecular mechanisms of mammalian autophagy initiation by the ULK complex. © 2015 Nature America, Inc. All rights reserved.


Noda N.N.,Institute of Microbial Chemistry BIKAKEN | Noda N.N.,Japan Science and Technology Agency | Fujioka Y.,Institute of Microbial Chemistry BIKAKEN
Cellular and Molecular Life Sciences | Year: 2015

Autophagosome formation, a landmark event in autophagy, is accomplished by the concerted actions of Atg proteins. Among all Atg proteins, Atg1 kinase in yeast and its counterpart in higher eukaryotes, ULK1 kinase, function as the most upstream factor in this process and mediate autophagy initiation. In this review, we summarize current knowledge of the structure, molecular function, and regulation of Atg1 family kinases in the initiation of autophagy. © 2015 The Author(s).


Ogawa T.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Japan Science and Technology Agency
Angewandte Chemie - International Edition | Year: 2013

Confined cat works better: A self-assembling heterobimetallic catalyst, comprised of a Nd/Na/amide ligand confined in an entangled multiwalled carbon nanotube (MWNT) network, outperforms the unconfined catalyst in anti-selective catalytic asymmetric nitroaldol reactions. The confined catalyst could be used repeatedly through simple filtration, and was applied to a concise enantioselective synthesis of anacetrapib. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Yin L.,Institute of Microbial Chemistry BIKAKEN | Takada H.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Japan Science and Technology Agency
Angewandte Chemie - International Edition | Year: 2013

A cooperative catalyst consisting of a soft Lewis acid and a hard Brønsted base promoted the title reaction. The N-thiophosphinoyl group on the ketimines was critical to surpass the high activation barrier through the soft-soft interaction of sulfur and copper. Mannich adducts with a tetrasubstituted stereogenic center were produced with excellent diastereo- and enantioselectivities. TANIAPHOS= ferrocenyl ligand. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Weidner K.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Japan Science and Technology Agency
Angewandte Chemie - International Edition | Year: 2014

The direct catalytic asymmetric aldol reaction offers efficient access to β-hydroxy carbonyl entities. Described is a robust direct catalytic asymmetric aldol reaction of α-sulfanyl 7-azaindolinylamide, thus affording both aromatic and aliphatic β-hydroxy amides with high ee values. The design of this transformation features a cooperative interplay of a soft and a hard Lewis acid, which together facilitate the challenging chemoselective enolization by a hard Brønsted base. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Yin L.,Institute of Microbial Chemistry BIKAKEN | Takada H.,Institute of Microbial Chemistry BIKAKEN | Lin S.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | And 2 more authors.
Angewandte Chemie - International Edition | Year: 2014

Soft Lewis acid/Brønsted base cooperative catalysts have enabled direct catalytic asymmetric vinylogous conjugate addition of α,β- and β,γ-unsaturated butyrolactones to α,β-unsaturated thioamides with perfect atom economy. When using α-angelica lactone and its derivatives as pronucleophiles, as little as 0.5 mol % catalyst loading was sufficient to complete the reaction necessary to construct consecutive tri- and tetrasubstituted stereogenic centers in a highly diastereo- and enantioselective fashion. Soft spot: Soft Lewis acid/Brønsted base cooperative catalysts have enabled the title reaction of α,β- and β,γ- unsaturated butyrolactones with perfect atom economy. When using α-angelica lactone and its derivatives as pronucleophiles, a 0.5 mol % catalyst loading was sufficient to complete the reaction to construct consecutive tri- and tetrasubstituted stereogenic centers in a highly diastereo- and enantioselective fashion. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Yin L.,Institute of Microbial Chemistry BIKAKEN | Bao Y.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Japan Science and Technology Agency
Journal of the American Chemical Society | Year: 2013

Catalytic asymmetric hydrophosphonylation of aromatic and aliphatic N-thiophosphinoyl ketimines with dialkyl phosphite was efficiently promoted by as little as 0.5 mol% of catalyst loading at ambient temperature. The catalyst can be recovered for repeated use, and facile removal of the thiophosphinoyl group allowed for ready access to the phosphonic acid analogue of enantioenriched α,α-disubstituted α-amino acids. © 2013 American Chemical Society.


Lin S.,Institute of Microbial Chemistry BIKAKEN | Kawato Y.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Japan Science and Technology Agency
Angewandte Chemie - International Edition | Year: 2015

Optically active vicinal diamines are versatile chiral building blocks in organic synthesis. A soft Lewis acid/hard Brønsted base cooperative catalyst allows for an efficient stereoselective coupling of N-alkylidene-α-aminoacetonitrile and ketimines to access this class of compounds bearing consecutive tetra- and trisubstituted stereogenic centers. The strategic use of a soft Lewis basic thiophosphinoyl group for ketimines is the key to promoting the reaction, and aliphatic ketimines serve as suitable substrates with as little as 3 mol % catalyst loading. Getting in key: A soft Lewis acid/hard Brønsted base cooperative catalyst allows for efficient stereoselectives coupling of N-alkylidene-α-aminoacetonitrile and aliphatic ketimines to access vicinal diamines bearing consecutive tetra- and trisubstituted stereogenic centers. The use of a soft Lewis basic thiophosphinoyl group on the ketimines is key to promoting the reaction with as little as 3 mol % catalyst loading. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Hashimoto K.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Japan Science and Technology Agency
Organic Letters | Year: 2014

An anti-selective catalytic asymmetric nitroaldol reaction was manifested in a continuous-flow platform. The requisite Nd/Na heterogeneous catalyst was readily prepared by self-assembly of an amide-based chiral ligand, NdO 1/5(OiPr)13/5, NaHMDS, and a multiwalled carbon nanotube without covalent linkage. A stainless-steel column filled with the Nd/Na catalyst was incorporated in a flow system to promote the nitroaldol reaction with high stereoselectivity. The flow system with the heterogeneous catalyst obviated the quenching operation, and the cooling system was minimized. © 2014 American Chemical Society.

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