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| | <StructureSection load='3fvu' size='340' side='right'caption='[[3fvu]], [[Resolution|resolution]] 1.55Å' scene=''> | | <StructureSection load='3fvu' size='340' side='right'caption='[[3fvu]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3fvu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FVU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3fvu]] is a 2 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=3FVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FVU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IAC:1H-INDOL-3-YLACETIC+ACID'>IAC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IAC:1H-INDOL-3-YLACETIC+ACID'>IAC</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=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3fvs|3fvs]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCBL1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3fvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fvu OCA], [https://pdbe.org/3fvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fvu RCSB], [https://www.ebi.ac.uk/pdbsum/3fvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fvu ProSAT]</span></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=3fvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fvu OCA], [https://pdbe.org/3fvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fvu RCSB], [https://www.ebi.ac.uk/pdbsum/3fvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fvu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/KAT1_HUMAN KAT1_HUMAN]] Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). Metabolizes the cysteine conjugates of certain halogenated alkenes and alkanes to form reactive metabolites. Catalyzes the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond.<ref>PMID:19338303</ref>
| + | [https://www.uniprot.org/uniprot/KAT1_HUMAN KAT1_HUMAN] Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). Metabolizes the cysteine conjugates of certain halogenated alkenes and alkanes to form reactive metabolites. Catalyzes the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond.<ref>PMID:19338303</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cai, T]] | + | [[Category: Cai T]] |
| - | [[Category: Han, Q]] | + | [[Category: Han Q]] |
| - | [[Category: Li, J]] | + | [[Category: Li J]] |
| - | [[Category: Robinson, H]] | + | [[Category: Robinson H]] |
| - | [[Category: Tagle, D A]] | + | [[Category: Tagle DA]] |
| - | [[Category: Alpha beta protein]]
| + | |
| - | [[Category: Aminotransferase]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Plp dependent protein]]
| + | |
| - | [[Category: Pyridoxal phosphate]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
KAT1_HUMAN Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). Metabolizes the cysteine conjugates of certain halogenated alkenes and alkanes to form reactive metabolites. Catalyzes the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond.[1]
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 PubMed
Human kynurenine aminotransferase I (hKAT I) catalyzes the formation of kynurenic acid, a neuroactive compound. Here, we report three high-resolution crystal structures (1.50-1.55 A) of hKAT I that are in complex with glycerol and each of two inhibitors of hKAT I: indole-3-acetic acid (IAC) and Tris. Because Tris is able to occupy the substrate binding position, we speculate that this may be the basis for hKAT I inhibition. Furthermore, the hKAT/IAC complex structure reveals that the binding moieties of the inhibitor are its indole ring and a carboxyl group. Six chemicals with both binding moieties were tested for their ability to inhibit hKAT I activity; 3-indolepropionic acid and DL-indole-3-lactic acid demonstrated the highest level of inhibition, and as they cannot be considered as substrates of the enzyme, these two inhibitors are promising candidates for future study. Perhaps even more significantly, we report the discovery of two different ligands located simultaneously in the hKAT I active center for the first time.
Structural insight into the inhibition of human kynurenine aminotransferase I/glutamine transaminase K.,Han Q, Robinson H, Cai T, Tagle DA, Li J J Med Chem. 2009 May 14;52(9):2786-93. PMID:19338303[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Han Q, Robinson H, Cai T, Tagle DA, Li J. Structural insight into the inhibition of human kynurenine aminotransferase I/glutamine transaminase K. J Med Chem. 2009 May 14;52(9):2786-93. PMID:19338303 doi:10.1021/jm9000874
- ↑ Han Q, Robinson H, Cai T, Tagle DA, Li J. Structural insight into the inhibition of human kynurenine aminotransferase I/glutamine transaminase K. J Med Chem. 2009 May 14;52(9):2786-93. PMID:19338303 doi:10.1021/jm9000874
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