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| | ==Crystal Structure of Human Catechol O-Methyltransferase with bound SAM and DNC== | | ==Crystal Structure of Human Catechol O-Methyltransferase with bound SAM and DNC== |
| - | <StructureSection load='3bwm' size='340' side='right' caption='[[3bwm]], [[Resolution|resolution]] 1.98Å' scene=''> | + | <StructureSection load='3bwm' size='340' side='right'caption='[[3bwm]], [[Resolution|resolution]] 1.98Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3bwm]] 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=3BWM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BWM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3bwm]] 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=3BWM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BWM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DNC:3,5-DINITROCATECHOL'>DNC</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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]] 1.98Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">COMT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DNC:3,5-DINITROCATECHOL'>DNC</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=3bwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bwm OCA], [https://pdbe.org/3bwm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bwm RCSB], [https://www.ebi.ac.uk/pdbsum/3bwm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bwm ProSAT]</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=3bwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bwm OCA], [http://pdbe.org/3bwm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bwm RCSB], [http://www.ebi.ac.uk/pdbsum/3bwm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3bwm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/COMT_HUMAN COMT_HUMAN]] 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_HUMAN COMT_HUMAN] 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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bw/3bwm_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bw/3bwm_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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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: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Parson, W W]] | + | [[Category: Large Structures]] |
| - | [[Category: Rutherford, K]]
| + | [[Category: Le Trong I]] |
| - | [[Category: Stenkamp, R E]]
| + | [[Category: Parson WW]] |
| - | [[Category: Trong, I Le]] | + | [[Category: Rutherford K]] |
| - | [[Category: Alternative initiation]] | + | [[Category: Stenkamp RE]] |
| - | [[Category: Catecholamine metabolism]] | + | |
| - | [[Category: Comt]] | + | |
| - | [[Category: Dnc]]
| + | |
| - | [[Category: Magnesium]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Neurotransmitter degradation]]
| + | |
| - | [[Category: Rossmann fold]]
| + | |
| - | [[Category: S-adenosyl-l-methionine]]
| + | |
| - | [[Category: Sam]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
Function
COMT_HUMAN 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.
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
Catechol O-methyltransferase (COMT) plays important roles in the metabolism of catecholamine neurotransmitters and catechol estrogens. The development of COMT inhibitors for use in the treatment of Parkinson's disease has been aided by crystallographic structures of the rat enzyme. However, the human and rat proteins have significantly different substrate specificities. Additionally, human COMT contains a common valine-methionine polymorphism at position 108. The methionine protein is less stable than the valine polymorph, resulting in decreased enzyme activity and protein levels in vivo. Here we describe the crystal structures of the 108V and 108M variants of the soluble form of human COMT bound with S-adenosylmethionine (SAM) and a substrate analog, 3,5-dinitrocatechol. The polymorphic residue 108 is located in the alpha5-beta3 loop, buried in a hydrophobic pocket approximately 16 A from the SAM-binding site. The 108V and 108M structures are very similar overall [RMSD of C(alpha) atoms between two structures (C(alpha) RMSD)=0.2 A], and the active-site residues are superposable, in accord with the observation that SAM stabilizes 108M COMT. However, the methionine side chain is packed more tightly within the polymorphic site and, consequently, interacts more closely with residues A22 (alpha2) and R78 (alpha4) than does valine. These interactions of the larger methionine result in a 0.7-A displacement in the backbone structure near residue 108, which propagates along alpha1 and alpha5 toward the SAM-binding site. Although the overall secondary structures of the human and rat proteins are very similar (C(alpha) RMSD=0.4 A), several nonconserved residues are present in the SAM-(I89M, I91M, C95Y) and catechol- (C173V, R201M, E202K) binding sites. The human protein also contains three additional solvent-exposed cysteine residues (C95, C173, C188) that may contribute to intermolecular disulfide bond formation and protein aggregation.
Crystal structures of human 108V and 108M catechol O-methyltransferase.,Rutherford K, Le Trong I, Stenkamp RE, Parson WW J Mol Biol. 2008 Jun 27;380(1):120-30. Epub 2008 Apr 23. PMID:18486144[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rutherford K, Le Trong I, Stenkamp RE, Parson WW. Crystal structures of human 108V and 108M catechol O-methyltransferase. J Mol Biol. 2008 Jun 27;380(1):120-30. Epub 2008 Apr 23. PMID:18486144 doi:10.1016/j.jmb.2008.04.040
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