1hnn

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[[Image:1hnn.jpg|left|200px]]
 
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==CRYSTAL STRUCTURE OF HUMAN PNMT COMPLEXED WITH SK&F 29661 AND ADOHCY(SAH)==
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The line below this paragraph, containing "STRUCTURE_1hnn", creates the "Structure Box" on the page.
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<StructureSection load='1hnn' size='340' side='right'caption='[[1hnn]], [[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'>[[1hnn]] 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=1HNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HNN FirstGlance]. <br>
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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=SKF:1,2,3,4-TETRAHYDRO-ISOQUINOLINE-7-SULFONIC+ACID+AMIDE'>SKF</scene></td></tr>
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{{STRUCTURE_1hnn| PDB=1hnn | 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=1hnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hnn OCA], [https://pdbe.org/1hnn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hnn RCSB], [https://www.ebi.ac.uk/pdbsum/1hnn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hnn 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/hn/1hnn_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=1hnn ConSurf].
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<div style="clear:both"></div>
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'''CRYSTAL STRUCTURE OF HUMAN PNMT COMPLEXED WITH SK&F 29661 AND ADOHCY(SAH)'''
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==See Also==
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*[[Phenylethanolamine N-methyltransferase|Phenylethanolamine N-methyltransferase]]
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__TOC__
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==Overview==
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</StructureSection>
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BACKGROUND: Adrenaline is localized to specific regions of the central nervous system (CNS), but its role therein is unclear because of a lack of suitable pharmacologic agents. Ideally, a chemical is required that crosses the blood-brain barrier, potently inhibits the adrenaline-synthesizing enzyme PNMT, and does not affect other catecholamine processes. Currently available PNMT inhibitors do not meet these criteria. We aim to produce potent, selective, and CNS-active PNMT inhibitors by structure-based design methods. The first step is the structure determination of PNMT. RESULTS: We have solved the crystal structure of human PNMT complexed with a cofactor product and a submicromolar inhibitor at a resolution of 2.4 A. The structure reveals a highly decorated methyltransferase fold, with an active site protected from solvent by an extensive cover formed from several discrete structural motifs. The structure of PNMT shows that the inhibitor interacts with the enzyme in a different mode from the (modeled) substrate noradrenaline. Specifically, the position and orientation of the amines is not equivalent. CONCLUSIONS: An unexpected finding is that the structure of PNMT provides independent evidence of both backward evolution and fold recruitment in the evolution of a complex enzyme from a simple fold. The proposed evolutionary pathway implies that adrenaline, the product of PNMT catalysis, is a relative newcomer in the catecholamine family. The PNMT structure reported here enables the design of potent and selective inhibitors with which to characterize the role of adrenaline in the CNS. Such chemical probes could potentially be useful as novel therapeutics.
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==Disease==
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Known disease associated with this structure: Hypertension, essential, 145500 (1) OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=171190 171190]]
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==About this Structure==
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1HNN 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=1HNN OCA].
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==Reference==
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Getting the adrenaline going: crystal structure of the adrenaline-synthesizing enzyme PNMT., Martin JL, Begun J, McLeish MJ, Caine JM, Grunewald GL, Structure. 2001 Oct;9(10):977-85. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11591352 11591352]
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[[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: Begun J]]
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[[Category: Begun, J.]]
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[[Category: Caine JM]]
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[[Category: Caine, J M.]]
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[[Category: Grunewald GL]]
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[[Category: Grunewald, G L.]]
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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: Adrenaline synthesis]]
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[[Category: Methyltransferase]]
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[[Category: S-adenosyl methionine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:02:48 2008''
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Current revision

CRYSTAL STRUCTURE OF HUMAN PNMT COMPLEXED WITH SK&F 29661 AND ADOHCY(SAH)

PDB ID 1hnn

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