6t8q: Difference between revisions
New page: '''Unreleased structure''' The entry 6t8q is ON HOLD Authors: Description: Category: Unreleased Structures |
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==HKATII IN COMPLEX WITH LIGAND (2R)-N-benzyl-1-[6-methyl-5-(oxan-4-yl)-7-oxo-6H,7H-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide== | |||
<StructureSection load='6t8q' size='340' side='right'caption='[[6t8q]], [[Resolution|resolution]] 2.51Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6t8q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T8Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T8Q FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.51Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene>, <scene name='pdbligand=MVQ:(2~{R})-1-[6-methyl-5-(oxan-4-yl)-7-oxidanylidene-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-~{N}-(phenylmethyl)pyrrolidine-2-carboxamide'>MVQ</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6t8q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t8q OCA], [https://pdbe.org/6t8q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t8q RCSB], [https://www.ebi.ac.uk/pdbsum/6t8q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t8q ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AADAT_HUMAN AADAT_HUMAN] Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino-group acceptors, with a preference for 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxylate as amino-group acceptor (in vitro).<ref>PMID:18620547</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human kynurenine aminotransferase 2 (KAT2) inhibitors could be potentially used to treat the cognitive deficits associated with bipolar disease and schizophrenia. Although, there has been active drug research activity by several industrial and academic groups in developing KAT2 inhibitors over the years, no such compound has proceeded to the clinics. Here, we report two different chemical series of reversible KAT2 inhibitors with sub-micromolar activities. The first series was identified by a high-throughput screening of a diverse random library and the second one by structure-based virtual screening. Two novel crystal structures of KAT2 complexed with different reversible inhibitors were also deposited to the Protein databank which could be useful for future drug discovery efforts. | |||
Discovery of sulfonamides and 9-oxo-2,8-diazaspiro[5,5]undecane-2-carboxamides as human kynurenine aminotransferase 2 (KAT2) inhibitors.,Kalliokoski T, Rummakko P, Rantanen M, Blaesse M, Augustin M, Ummenthala GR, Choudhary S, Venalainen J Bioorg Med Chem Lett. 2020 Feb 22:127060. doi: 10.1016/j.bmcl.2020.127060. PMID:32113843<ref>PMID:32113843</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6t8q" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Aminotransferase 3D structures|Aminotransferase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Blaesse M]] | |||
[[Category: Venalainen J]] | |||
Latest revision as of 15:57, 24 January 2024
HKATII IN COMPLEX WITH LIGAND (2R)-N-benzyl-1-[6-methyl-5-(oxan-4-yl)-7-oxo-6H,7H-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamideHKATII IN COMPLEX WITH LIGAND (2R)-N-benzyl-1-[6-methyl-5-(oxan-4-yl)-7-oxo-6H,7H-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide
Structural highlights
FunctionAADAT_HUMAN Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino-group acceptors, with a preference for 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxylate as amino-group acceptor (in vitro).[1] Publication Abstract from PubMedHuman kynurenine aminotransferase 2 (KAT2) inhibitors could be potentially used to treat the cognitive deficits associated with bipolar disease and schizophrenia. Although, there has been active drug research activity by several industrial and academic groups in developing KAT2 inhibitors over the years, no such compound has proceeded to the clinics. Here, we report two different chemical series of reversible KAT2 inhibitors with sub-micromolar activities. The first series was identified by a high-throughput screening of a diverse random library and the second one by structure-based virtual screening. Two novel crystal structures of KAT2 complexed with different reversible inhibitors were also deposited to the Protein databank which could be useful for future drug discovery efforts. Discovery of sulfonamides and 9-oxo-2,8-diazaspiro[5,5]undecane-2-carboxamides as human kynurenine aminotransferase 2 (KAT2) inhibitors.,Kalliokoski T, Rummakko P, Rantanen M, Blaesse M, Augustin M, Ummenthala GR, Choudhary S, Venalainen J Bioorg Med Chem Lett. 2020 Feb 22:127060. doi: 10.1016/j.bmcl.2020.127060. PMID:32113843[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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