5x2l: Difference between revisions
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==Crystal Structure of Human Serine Racemase== | |||
<StructureSection load='5x2l' size='340' side='right' caption='[[5x2l]], [[Resolution|resolution]] 1.81Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5x2l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X2L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X2L FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5x2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x2l OCA], [http://pdbe.org/5x2l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x2l RCSB], [http://www.ebi.ac.uk/pdbsum/5x2l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x2l ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/SRR_HUMAN SRR_HUMAN]] Catalyzes the synthesis of D-serine from L-serine. D-serine is a key coagonist with glutamate at NMDA receptors. Has dehydratase activity towards both L-serine and D-serine.<ref>PMID:11054547</ref> <ref>PMID:20106978</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Most of the endogenous free d-serine (about 90%) in the brain is produced by serine racemase (SR). d-Serine in the brain is involved in neurodegenerative disorders and epileptic states as an endogenous co-agonist of the NMDA-type glutamate receptor. Thus, SR inhibitors are expected to be novel therapeutic candidates for the treatment of these disorders. In this study, we solved the crystal structure of wild-type SR, and tried to identify a new inhibitor of SR by in silico screening using the structural information. As a result, we identified two hit compounds by their in vitro evaluations using wild-type SR. Based on the structure of the more potent hit compound 1, we synthesized 15 derivatives and evaluated their inhibitory activities against wild-type SR. Among them, the compound 9C showed relatively high inhibitory potency for wild-type SR. Compound 9C was a more potent inhibitor than compound 24, which was synthesized by our group based upon the structural information of the mutant-type SR. | |||
Design, synthesis, and evaluation of novel inhibitors for wild-type human serine racemase.,Takahara S, Nakagawa K, Uchiyama T, Yoshida T, Matsumoto K, Kawasumi Y, Mizuguchi M, Obita T, Watanabe Y, Hayakawa D, Gouda H, Mori H, Toyooka N Bioorg Med Chem Lett. 2017 Dec 13. pii: S0960-894X(17)31180-0. doi:, 10.1016/j.bmcl.2017.12.021. PMID:29277459<ref>PMID:29277459</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5x2l" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Matsumoto, K]] | |||
[[Category: Mizuguchi, M]] | |||
[[Category: Mori, H]] | |||
[[Category: Obita, T]] | |||
[[Category: Toyooka, N]] | |||
[[Category: Human]] | |||
[[Category: Isomerase]] | |||
[[Category: Lyase]] | |||
[[Category: Pyridoxal-5'-phosphate]] | |||
[[Category: Serine racemase]] | |||
Revision as of 05:53, 31 January 2018
Crystal Structure of Human Serine Racemase
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