2g71: Difference between revisions

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-[[Image:2g71.png|left|200px]]
-<!--
+==Structure of hPNMT with inhibitor 3-fluoromethyl-7-trifluoropropyl-THIQ and AdoHcy==
-The line below this paragraph, containing "STRUCTURE_2g71", creates the "Structure Box" on the page.
+<StructureSection load='2g71' size='340' side='right'caption='[[2g71]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2g71]] 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=2G71 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2G71 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FTS:(3R)-3-(FLUOROMETHYL)-N-(3,3,3-TRIFLUOROPROPYL)-1,2,3,4-TETRAHYDROISOQUINOLINE-7-SULFONAMIDE'>FTS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
-{{STRUCTURE_2g71|  PDB=2g71  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2g71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g71 OCA], [https://pdbe.org/2g71 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2g71 RCSB], [https://www.ebi.ac.uk/pdbsum/2g71 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2g71 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PNMT_HUMAN PNMT_HUMAN] Converts noradrenaline to adrenaline.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g7/2g71_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=2g71 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Shape complementarity is a fundamental principle of inhibitor design. Here we show that an enzyme for which the crystal structure has been determined (phenylethanolamine N-methyltransferase, PNMT) conceals a cryptic binding site. This site is revealed upon binding of inhibitors that are double the size of the physiological substrate. These large inhibitors are not predicted to bind in that they protrude through the accessible surface calculated from a PNMT/7-aminosulfonyl-1,2,3,4-tetrahydroisoquinoline (SK&amp;F 29661) crystal structure, yet they are potent inhibitors of PNMT. We determined structures of the enzyme complexed with large inhibitors and found that the volume of the active site increases by 140 A3 upon binding. Changes in active site size and shape are brought about by unfavorable side chain conformations and rigid body helix motions. The energetic cost is modest, estimated at 2-3 kcal/mol from mutational analyses. Our findings further underline the importance of protein flexibility in structure-based inhibitor design studies.
-===Structure of hPNMT with inhibitor 3-fluoromethyl-7-trifluoropropyl-THIQ and AdoHcy===
+Enzyme adaptation to inhibitor binding: a cryptic binding site in phenylethanolamine N-methyltransferase.,Gee CL, Drinkwater N, Tyndall JD, Grunewald GL, Wu Q, McLeish MJ, Martin JL J Med Chem. 2007 Oct 4;50(20):4845-53. Epub 2007 Sep 11. PMID:17845018<ref>PMID:17845018</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_17845018}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 2g71" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 17845018 is the PubMed ID number.
--->
-{{ABSTRACT_PUBMED_17845018}}
-==About this Structure==
-[[2g71]] is a 2 chain structure of [[Phenylethanolamine N-methyltransferase]] 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=2G71 OCA].
 ==See Also==
-*[[Phenylethanolamine N-methyltransferase]]
+*[[Phenylethanolamine N-methyltransferase|Phenylethanolamine N-methyltransferase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:17845018</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Phenylethanolamine N-methyltransferase]]
+[[Category: Large Structures]]
-[[Category: Gee, C L.]]
+[[Category: Gee CL]]
-[[Category: Martin, J L.]]
+[[Category: Martin JL]]
-[[Category: Tyndall, J D.A.]]
+[[Category: Tyndall JDA]]
-[[Category: Methyltransferase]]