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| | <StructureSection load='4p58' size='340' side='right'caption='[[4p58]], [[Resolution|resolution]] 2.06Å' scene=''> | | <StructureSection load='4p58' size='340' side='right'caption='[[4p58]], [[Resolution|resolution]] 2.06Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4p58]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P58 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P58 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4p58]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P58 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P58 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2F6:1,3-DIMETHYL-1H,1H-3,4-BIPYRAZOLE'>2F6</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2F6:1,3-DIMETHYL-1H,1H-3,4-BIPYRAZOLE'>2F6</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Comt, Comt1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4p58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p58 OCA], [https://pdbe.org/4p58 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p58 RCSB], [https://www.ebi.ac.uk/pdbsum/4p58 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p58 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Catechol_O-methyltransferase Catechol O-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.6 2.1.1.6] </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=4p58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p58 OCA], [http://pdbe.org/4p58 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p58 RCSB], [http://www.ebi.ac.uk/pdbsum/4p58 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p58 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/COMT_MOUSE COMT_MOUSE]] Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol. | + | [https://www.uniprot.org/uniprot/COMT_MOUSE COMT_MOUSE] Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Catechol O-methyltransferase|Catechol O-methyltransferase]] | + | *[[Catechol O-methyltransferase 3D structures|Catechol O-methyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Catechol O-methyltransferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Lanier, M]] | + | [[Category: Lanier M]] |
| - | [[Category: Sam binding site]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
Function
COMT_MOUSE Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
Publication Abstract from PubMed
Catechol O-methyl transferase belongs to the diverse family of S-adenosyl-l-methionine transferases. It is a target involved in the treatment of Parkinson's disease. Here we present a fragment-based screening approach to discover noncatechol derived COMT inhibitors which bind at the SAM binding pocket. We describe the identification and characterization of a series of highly ligand efficient SAM competitive bisaryl fragments (LE = 0.33-0.58). We also present the first SAM-competitive small-molecule COMT co-complex crystal structure.
A Fragment-Based Approach to Identifying S-Adenosyl-l-methionine -Competitive Inhibitors of Catechol O-Methyl Transferase (COMT).,Lanier M, Ambrus G, Cole DC, Davenport R, Ellery J, Fosbeary R, Jennings AJ, Kadotani A, Kamada Y, Kamran R, Matsumoto SI, Mizukami A, Okubo S, Okada K, Saikatendu K, Walsh L, Wu H, Hixon MS J Med Chem. 2014 Jun 4. PMID:24847974[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lanier M, Ambrus G, Cole DC, Davenport R, Ellery J, Fosbeary R, Jennings AJ, Kadotani A, Kamada Y, Kamran R, Matsumoto SI, Mizukami A, Okubo S, Okada K, Saikatendu K, Walsh L, Wu H, Hixon MS. A Fragment-Based Approach to Identifying S-Adenosyl-l-methionine -Competitive Inhibitors of Catechol O-Methyl Transferase (COMT). J Med Chem. 2014 Jun 4. PMID:24847974 doi:http://dx.doi.org/10.1021/jm500475k
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