1yz3

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[[Image:1yz3.gif|left|200px]]
 
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==Structure of human pnmt complexed with cofactor product adohcy and inhibitor SK&F 64139==
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The line below this paragraph, containing "STRUCTURE_1yz3", creates the "Structure Box" on the page.
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<StructureSection load='1yz3' size='340' side='right'caption='[[1yz3]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1yz3]] 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=1YZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YZ3 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SKA:7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE'>SKA</scene></td></tr>
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{{STRUCTURE_1yz3| PDB=1yz3 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1yz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yz3 OCA], [https://pdbe.org/1yz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yz3 RCSB], [https://www.ebi.ac.uk/pdbsum/1yz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yz3 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PNMT_HUMAN PNMT_HUMAN] Converts noradrenaline to adrenaline.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yz/1yz3_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1yz3 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The X-ray structure of human phenylethanolamine N-methyltransferase (hPNMT) complexed with its product, S-adenosyl-L-homocysteine (4), and the most potent inhibitor reported to date, SK&amp;F 64139 (7), was used to identify the residues involved in inhibitor binding. Four of these residues, Val53, Lys57, Glu219 and Asp267, were replaced, in turn, with alanine. All variants had increased Km values for phenylethanolamine (10), but only D267A showed a noteworthy (20-fold) decrease in its kcat value. Both WT hPNMT and D267A had similar kcat values for a rigid analogue, anti-9-amino-6-(trifluoromethyl)benzonorbornene (12), suggesting that Asp267 plays an important role in positioning the substrate but does not participate directly in catalysis. The Ki values for the binding of inhibitors such as 7 to the E219A and D267A variants increased by 2-3 orders of magnitude. Further, the inhibitors were shown to bind up to 50-fold more tightly in the presence of S-adenosyl-L-methionine (3), suggesting that the binding of the latter brings about a conformational change in the enzyme.
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'''Structure of human pnmt complexed with cofactor product adohcy and inhibitor SK&F 64139'''
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Structural, mutagenic, and kinetic analysis of the binding of substrates and inhibitors of human phenylethanolamine N-methyltransferase.,Wu Q, Gee CL, Lin F, Tyndall JD, Martin JL, Grunewald GL, McLeish MJ J Med Chem. 2005 Nov 17;48(23):7243-52. PMID:16279783<ref>PMID:16279783</ref>
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==Overview==
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The X-ray structure of human phenylethanolamine N-methyltransferase (hPNMT) complexed with its product, S-adenosyl-L-homocysteine (4), and the most potent inhibitor reported to date, SK&amp;F 64139 (7), was used to identify the residues involved in inhibitor binding. Four of these residues, Val53, Lys57, Glu219 and Asp267, were replaced, in turn, with alanine. All variants had increased Km values for phenylethanolamine (10), but only D267A showed a noteworthy (20-fold) decrease in its kcat value. Both WT hPNMT and D267A had similar kcat values for a rigid analogue, anti-9-amino-6-(trifluoromethyl)benzonorbornene (12), suggesting that Asp267 plays an important role in positioning the substrate but does not participate directly in catalysis. The Ki values for the binding of inhibitors such as 7 to the E219A and D267A variants increased by 2-3 orders of magnitude. Further, the inhibitors were shown to bind up to 50-fold more tightly in the presence of S-adenosyl-L-methionine (3), suggesting that the binding of the latter brings about a conformational change in the enzyme.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1YZ3 is a [[Single protein]] structure of 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=1YZ3 OCA].
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</div>
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<div class="pdbe-citations 1yz3" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Structural, mutagenic, and kinetic analysis of the binding of substrates and inhibitors of human phenylethanolamine N-methyltransferase., Wu Q, Gee CL, Lin F, Tyndall JD, Martin JL, Grunewald GL, McLeish MJ, J Med Chem. 2005 Nov 17;48(23):7243-52. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16279783 16279783]
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*[[Phenylethanolamine N-methyltransferase|Phenylethanolamine N-methyltransferase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Phenylethanolamine N-methyltransferase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Gee CL]]
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[[Category: Gee, C L.]]
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[[Category: Grunewald GL]]
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[[Category: Grunewald, G L.]]
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[[Category: Lin F]]
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[[Category: Lin, F.]]
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[[Category: Martin JL]]
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[[Category: Martin, J L.]]
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[[Category: McLeish MJ]]
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[[Category: McLeish, M J.]]
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[[Category: Wu Q]]
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[[Category: Wu, Q.]]
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[[Category: Enzyme]]
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[[Category: Inhibitor complex]]
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[[Category: Product]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:59:10 2008''
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Current revision

Structure of human pnmt complexed with cofactor product adohcy and inhibitor SK&F 64139

PDB ID 1yz3

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