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==Humanized rat apo-COMT in complex with a ureido-benzamidine==
==Humanized rat apo-COMT in complex with a ureido-benzamidine==
<StructureSection load='4pyq' size='340' side='right' caption='[[4pyq]], [[Resolution|resolution]] 1.39&Aring;' scene=''>
<StructureSection load='4pyq' size='340' side='right'caption='[[4pyq]], [[Resolution|resolution]] 1.39&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4pyq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PYQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PYQ FirstGlance]. <br>
<table><tr><td colspan='2'>[[4pyq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PYQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PYQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2X1:4-({[3-(AMINOMETHYL)PHENYL]CARBAMOYL}AMINO)BENZENECARBOXIMIDAMIDE'>2X1</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2X1:4-({[3-(AMINOMETHYL)PHENYL]CARBAMOYL}AMINO)BENZENECARBOXIMIDAMIDE'>2X1</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4p7k|4p7k]], [[4p7f|4p7f]], [[4p7g|4p7g]], [[4p7j|4p7j]], [[4pyj|4pyj]], [[4pyi|4pyi]], [[4pyk|4pyk]], [[4pyl|4pyl]], [[4pym|4pym]], [[4pyn|4pyn]], [[4pyo|4pyo]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4p7k|4p7k]], [[4p7f|4p7f]], [[4p7g|4p7g]], [[4p7j|4p7j]], [[4pyj|4pyj]], [[4pyi|4pyi]], [[4pyk|4pyk]], [[4pyl|4pyl]], [[4pym|4pym]], [[4pyn|4pyn]], [[4pyo|4pyo]]</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=10116 Buffalo rat])</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='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=4pyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyq OCA], [http://pdbe.org/4pyq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pyq RCSB], [http://www.ebi.ac.uk/pdbsum/4pyq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pyq 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=4pyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyq OCA], [http://pdbe.org/4pyq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pyq RCSB], [http://www.ebi.ac.uk/pdbsum/4pyq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pyq ProSAT]</span></td></tr>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Buffalo rat]]
[[Category: Catechol O-methyltransferase]]
[[Category: Catechol O-methyltransferase]]
[[Category: Large Structures]]
[[Category: Benz, J]]
[[Category: Benz, J]]
[[Category: Ehler, A]]
[[Category: Ehler, A]]

Revision as of 11:12, 17 April 2019

Humanized rat apo-COMT in complex with a ureido-benzamidineHumanized rat apo-COMT in complex with a ureido-benzamidine

Structural highlights

4pyq is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , ,
Gene:Comt (Buffalo rat)
Activity:Catechol O-methyltransferase, with EC number 2.1.1.6
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[COMT_RAT] 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

Methylation catalysed by catechol-O-methyltransferase (COMT) is the main pathway of catechol neurotransmitter deactivation in the prefrontal cortex. Low levels of this class of neurotransmitters are held to be causative of diseases such as schizophrenia, depression and Parkinson's disease. Inhibition of COMT may increase neurotransmitter levels, thus offering a route for treatment. Structure-based drug design hitherto seems to be based on the closed enzyme conformation. Here, a set of apo, semi-holo, holo and Michaelis form crystal structures are described that define the conformational space available to COMT and that include likely intermediates along the catalytic pathway. Domain swaps and sizeable loop movements around the active site testify to the flexibility of this enzyme, rendering COMT a difficult drug target. The low affinity of the co-substrate S-adenosylmethionine and the large conformational changes involved during catalysis highlight significant energetic investment to achieve the closed conformation. Since each conformation of COMT is a bona fide target for inhibitors, other states than the closed conformation may be promising to address. Crystallographic data for an alternative avenue of COMT inhibition, i.e. locking of the apo state by an inhibitor, are presented. The set of COMT structures may prove to be useful for the development of novel classes of inhibitors.

Mapping the conformational space accessible to catechol-O-methyltransferase.,Ehler A, Benz J, Schlatter D, Rudolph MG Acta Crystallogr D Biol Crystallogr. 2014 Aug 1;70(Pt 8):2163-74. doi:, 10.1107/S1399004714012917. Epub 2014 Jul 25. PMID:25084335[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Ehler A, Benz J, Schlatter D, Rudolph MG. Mapping the conformational space accessible to catechol-O-methyltransferase. Acta Crystallogr D Biol Crystallogr. 2014 Aug 1;70(Pt 8):2163-74. doi:, 10.1107/S1399004714012917. Epub 2014 Jul 25. PMID:25084335 doi:http://dx.doi.org/10.1107/S1399004714012917

4pyq, resolution 1.39Å

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