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==X-ray crystal structure of human serine racemase in complex with malonate a potent inhibitor== | |||
<StructureSection load='3l6b' size='340' side='right' caption='[[3l6b]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3l6b]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L6B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L6B FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l6c|3l6c]], [[3l6r|3l6r]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SRR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Serine_racemase Serine racemase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.18 5.1.1.18] </span></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=3l6b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l6b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l6b RCSB], [http://www.ebi.ac.uk/pdbsum/3l6b PDBsum]</span></td></tr> | |||
</table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l6/3l6b_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding.,Smith MA, Mack V, Ebneth A, Moraes I, Felicetti B, Wood M, Schonfeld D, Mather O, Cesura A, Barker J J Biol Chem. 2010 Apr 23;285(17):12873-81. Epub 2010 Jan 27. PMID:20106978<ref>PMID:20106978</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Serine racemase]] | [[Category: Serine racemase]] | ||
[[Category: Barker, J | [[Category: Barker, J]] | ||
[[Category: Cesura, A | [[Category: Cesura, A]] | ||
[[Category: Ebneth, A | [[Category: Ebneth, A]] | ||
[[Category: Felicetti, B | [[Category: Felicetti, B]] | ||
[[Category: Mack, V | [[Category: Mack, V]] | ||
[[Category: Moraes, I | [[Category: Moraes, I]] | ||
[[Category: Smith, M A | [[Category: Smith, M A]] | ||
[[Category: Isomerase]] | [[Category: Isomerase]] | ||
[[Category: Plp]] | [[Category: Plp]] | ||
[[Category: Pyridoxal phosphate]] | [[Category: Pyridoxal phosphate]] | ||
Revision as of 19:21, 18 December 2014
X-ray crystal structure of human serine racemase in complex with malonate a potent inhibitorX-ray crystal structure of human serine racemase in complex with malonate a potent inhibitor
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSerine 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. The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding.,Smith MA, Mack V, Ebneth A, Moraes I, Felicetti B, Wood M, Schonfeld D, Mather O, Cesura A, Barker J J Biol Chem. 2010 Apr 23;285(17):12873-81. Epub 2010 Jan 27. PMID:20106978[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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