The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding.

The Journal of Biological Chemistry
Myron A SmithJohn Barker

Abstract

Serine racemase is responsible for the synthesis of D-serine, an endogenous co-agonist for N-methyl-D-aspartate receptor-type glutamate receptors (NMDARs). This pyridoxal 5'-phosphate-dependent enzyme is involved both in the reversible conversion of L- to D-serine and serine catabolism by alpha,beta-elimination of water, thereby regulating D-serine levels. Because D-serine affects NMDAR signaling throughout the brain, serine racemase is a promising target for the treatment of disorders related to NMDAR dysfunction. To provide a molecular basis for rational drug design the x-ray crystal structures of human and rat serine racemase were determined at 1.5- and 2.1-A resolution, respectively, and in the presence and absence of the orthosteric inhibitor malonate. The structures revealed a fold typical of beta-family pyridoxal 5'-phosphate enzymes, with both a large domain and a flexible small domain associated into a symmetric dimer, and indicated a ligand-induced rearrangement of the small domain that organizes the active site for specific turnover of the substrate.

References

Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·H WoloskerS H Snyder
May 20, 1999·Nature Structural Biology·A PerrakisV S Lamzin
Oct 26, 1999·Acta Crystallographica. Section D, Biological Crystallography·J W Pflugrath
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·J P MothetS H Snyder
May 22, 2002·The Journal of Biological Chemistry·Silas P CookIgnacio Rodríguez-Crespo
Feb 4, 2003·Nature Biotechnology·Daniel A ErlansonTom O'Brien
Nov 5, 2003·Biochemistry·Taro YamadaFusao Takusagawa
Nov 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yunlei YangShumin Duan
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Jan 1, 1996·Acta Crystallographica. Section D, Biological Crystallography·J P Abrahams, A G Leslie
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Feb 4, 2005·Protein Science : a Publication of the Protein Society·Lei SunZihe Rao
May 23, 2006·Cell·Aude PanatierStéphane H R Oliet
May 25, 2006·Current Topics in Medicinal Chemistry·Dean G Brown, Johannes J Krupp
Dec 25, 2007·Acta Crystallographica. Section A, Foundations of Crystallography·George M Sheldrick
Sep 25, 2008·Protein Expression and Purification·Hillary E HoffmanJan Konvalinka
Jan 2, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ran InoueHisashi Mori
Apr 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Livia BalanHerman Wolosker
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jul 31, 2009·The Journal of Biological Chemistry·Masaru GotoNobuyoshi Esaki

❮ Previous
Next ❯

Citations

Feb 9, 2012·Amino Acids·Tomokazu ItoTohru Yoshimura
Aug 1, 2012·Amino Acids·Herman Wolosker, Hisashi Mori
Dec 28, 2012·Amino Acids·Tomokazu ItoTohru Yoshimura
Sep 15, 2011·Chemical Reviews·Paola ContiCarlo De Micheli
Nov 1, 2012·Protein Engineering, Design & Selection : PEDS·Cyong-Yi WangAndrew H-J Wang
Oct 3, 2012·Neurology Research International·John P CrowMisty Thompson
Jun 15, 2011·Biochimica Et Biophysica Acta·Michael D Toney
Jan 13, 2011·Biochimica Et Biophysica Acta·Herman Wolosker
Nov 3, 2010·Biochimica Et Biophysica Acta·Alessio Peracchi, Andrea Mozzarelli
Jun 15, 2011·The FEBS Journal·Sakshibeedu Rajegowda BharathMattur Ramabhadrashastry Narasimha Murthy
Sep 3, 2013·The FEBS Journal·Marialaura MarchettiAndrea Mozzarelli
Feb 23, 2012·Journal of Neuroscience Research·Wei Wang, Steven W Barger
Sep 15, 2015·Biochemical and Biophysical Research Communications·Zhen QinZhengqiang Jiang
Dec 3, 2014·European Journal of Medicinal Chemistry·Barbora VorlováMartin Lepšík
Jul 3, 2015·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudia BeatoGabriele Costantino
Dec 21, 2011·Journal of Enzyme Inhibition and Medicinal Chemistry·Ratna SinghAndrea Mozzarelli
Feb 8, 2011·Neuropharmacology·Viviane LabrieJohn C Roder
May 6, 2014·Frontiers in Synaptic Neuroscience·Nadia CanuLoredano Pollegioni
Oct 22, 2014·Amino Acids·Marialaura MarchettiAndrea Mozzarelli
Jul 23, 2016·Applied Microbiology and Biotechnology·Christian FemmerSven Panke
Aug 6, 2016·The Biochemical Journal·Stefano BrunoAndrea Mozzarelli
Apr 2, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Fang WuHeinz Gehring
Feb 11, 2020·Acta Crystallographica. Section F, Structural Biology Communications·Chloe R KoulourisS Mark Roe
Nov 11, 2017·Extremophiles : Life Under Extreme Conditions·Masahito MurakamiYoko Nagata
May 10, 2018·Frontiers in Microbiology·Tomokazu ItoTohru Yoshimura
Mar 21, 2019·Frontiers in Molecular Biosciences·Jing LiangJianyong Li
Feb 27, 2016·Acta Crystallographica. Section F, Structural Biology Communications·Lingling ZouJun Fan
Jun 15, 2018·Scientific Reports·Andrea V CanosaAndrea Mozzarelli
Mar 29, 2019·Frontiers in Molecular Biosciences·Danielle L GrahamDavid B Berkowitz
Jan 29, 2019·Frontiers in Molecular Biosciences·Samanta RaboniAndrea Mozzarelli
Sep 25, 2020·Biochimica Et Biophysica Acta. Proteins and Proteomics·Annalisa MichielonStefano Bruno
Aug 7, 2019·Journal of Chemical Theory and Computation·Susanta DasDan T Major

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis is a form of of brain inflammation due to antibodies against NMDA receptors. Discover the latest research on anti-NMDA receptor encephalitis here.