View source for 2g71


==Structure of hPNMT with inhibitor 3-fluoromethyl-7-trifluoropropyl-THIQ and AdoHcy==
<StructureSection load='2g71' size='340' side='right'caption='[[2g71]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2g71]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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>
</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>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1hnn|1hnn]], [[1n7i|1n7i]], [[1n7j|1n7j]], [[1yz3|1yz3]], [[2g70|2g70]], [[2g72|2g72]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pnmt ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phenylethanolamine_N-methyltransferase Phenylethanolamine N-methyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.28 2.1.1.28] </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=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/initialview01.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.

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>
<div class="pdbe-citations 2g71" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phenylethanolamine N-methyltransferase|Phenylethanolamine N-methyltransferase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Phenylethanolamine N-methyltransferase]]
[[Category: Gee, C L]]
[[Category: Martin, J L]]
[[Category: Tyndall, J D.A]]
[[Category: Methyltransferase]]
[[Category: Transferase]]