Elucidation of inhibitor-binding pockets of d-amino acid oxidase using docking simulation and N-sulfanylethylanilide-based labeling technology

Organic & Biomolecular Chemistry
Taiki KohikiAkira Otaka

Abstract

Because of the relevance of d-serine (d-Ser) to schizophrenia, inhibitors of d-amino acid oxidase (DAO), which catalyzes degradation of d-Ser in the presence of flavin adenine dinucleotide (FAD), are expected to be anti-schizophrenia therapeutics. In this study, binding pockets of DAO to its inhibitor 4-bromo-3-nitrobenzoic acid were searched by combining in silico docking simulation and labeling experiments employing an N-sulfanylethylanilide-based labeling technology that we have developed. The results clearly demonstrated that there are two binding pockets: one is shared with d-Ser and FAD, and the other is an unexpected cleft between the subunits of a DAO dimer. These findings will provide insight to aid the development of new DAO inhibitors. In addition, it was also proved that our labeling technology could be applicable to elucidate the binding pockets of proteins.

References

Jul 1, 1997·Progress in Neurobiology·A Hashimoto, T Oka
Dec 4, 1998·Biological Psychiatry·G TsaiJ T Coyle
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·J P MothetS H Snyder
Apr 18, 2006·FEBS Letters·Gianluca MollaLoredano Polegioni
Jul 1, 1935·The Biochemical Journal·H A Krebs
Jan 25, 2007·Amino Acids·M J Scolari, G B Acosta
Jan 26, 2007·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·M P M BoksR S Kahn
Feb 17, 2007·Biochemical and Biophysical Research Communications·Tomoya KawazoeKiyoshi Fukui
Oct 10, 2007·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Tomoya KawazoeKiyoshi Fukui
Apr 2, 2008·Schizophrenia Research·Caroline MadeiraRogério Panizzutti
May 6, 2008·Bioorganic & Medicinal Chemistry Letters·Tim SpareyMary Beth Young
Jun 19, 2008·Molecular Psychiatry·P W J BurnetP J Harrison
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Sep 30, 2009·Molecular Psychiatry·L VerrallP J Harrison
Mar 3, 2010·Journal of Peptide Science : an Official Publication of the European Peptide Society·Mattan HurevichChaim Gilon
Jul 22, 2010·The Open Medicinal Chemistry Journal·Sean M SmithPeter H Hutson
Feb 5, 2011·Current Drug Targets·Jana Jirásková-VaníčkováJan Konvalinka
Feb 8, 2011·Neuropharmacology·Viviane LabrieJohn C Roder
Mar 3, 2011·Current Pharmaceutical Design·Dana V Ferraris, Takashi Tsukamoto
Jul 9, 2011·Chembiochem : a European Journal of Chemical Biology·Kohei SatoAkira Otaka
Jun 12, 2012·Accounts of Chemical Research·Takahiro Hayashi, Itaru Hamachi
Aug 3, 2012·Expert Review of Neurotherapeutics·Emerson A NunesSerdar M Dursun
Aug 29, 2012·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Akira OtakaAkira Shigenaga
Oct 9, 2012·Current Opinion in Clinical Nutrition and Metabolic Care·Inna RadzishevskyHerman Wolosker
Nov 3, 2012·Current Pharmaceutical Design·Silvia SacchiGianluca Molla
Apr 10, 2013·Journal of Medicinal Chemistry·Takeshi HondoMakoto Takeuchi
May 2, 2013·Journal of Medicinal Chemistry·Seth C HopkinsThomas H Large
Jul 9, 2014·Bioscience Reports·Ryan T Terry-LorenzoThomas H Large
Feb 17, 2015·Future Medicinal Chemistry·Ewan Smith, Ian Collins

❮ Previous
Next ❯

Citations

Jan 13, 2018·Frontiers in Molecular Biosciences·Giulia MurtasLoredano Pollegioni
Aug 14, 2019·Organic & Biomolecular Chemistry·Dóra Judit Kiss, György G Ferenczy
Dec 14, 2018·Frontiers in Molecular Biosciences·Loredano PollegioniGiulia Murtas
Nov 7, 2019·Chemical & Pharmaceutical Bulletin·Akira Shigenaga
Jun 28, 2018·Frontiers in Molecular Biosciences·Silvia SacchiGiulia Murtas
Feb 5, 2019·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Akira Shigenaga
Dec 5, 2019·Frontiers in Molecular Biosciences·Giulia MurtasLoredano Pollegioni

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.