2aox: Difference between revisions
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==Histamine Methyltransferase (Primary Variant T105) Complexed with the Acetylcholinesterase Inhibitor and Altzheimer's Disease Drug Tacrine== | ==Histamine Methyltransferase (Primary Variant T105) Complexed with the Acetylcholinesterase Inhibitor and Altzheimer's Disease Drug Tacrine== | ||
<StructureSection load='2aox' size='340' side='right' caption='[[2aox]], [[Resolution|resolution]] 3.12Å' scene=''> | <StructureSection load='2aox' size='340' side='right' caption='[[2aox]], [[Resolution|resolution]] 3.12Å' scene=''> | ||
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HNMT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HNMT ([http://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'>[http://en.wikipedia.org/wiki/Histamine_N-methyltransferase Histamine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.8 2.1.1.8] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histamine_N-methyltransferase Histamine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.8 2.1.1.8] </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=2aox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aox OCA], [http://pdbe.org/2aox PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2aox RCSB], [http://www.ebi.ac.uk/pdbsum/2aox PDBsum]</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=2aox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aox OCA], [http://pdbe.org/2aox PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2aox RCSB], [http://www.ebi.ac.uk/pdbsum/2aox PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2aox ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ao/2aox_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ao/2aox_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=2aox ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
Revision as of 10:22, 9 May 2018
Histamine Methyltransferase (Primary Variant T105) Complexed with the Acetylcholinesterase Inhibitor and Altzheimer's Disease Drug TacrineHistamine Methyltransferase (Primary Variant T105) Complexed with the Acetylcholinesterase Inhibitor and Altzheimer's Disease Drug Tacrine
Structural highlights
Function[HNMT_HUMAN] Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIn mammals, histamine action is terminated through metabolic inactivation by histamine N-methyltransferase (HNMT) and diamine oxidase. In addition to three well-studied pharmacological functions, smooth muscle contraction, increased vascular permeability, and stimulation of gastric acid secretion, histamine plays important roles in neurotransmission, immunomodulation, and regulation of cell proliferation. The histamine receptor H1 antagonist diphenhydramine, the antimalarial drug amodiaquine, the antifolate drug metoprine, and the anticholinesterase drug tacrine (an early drug for Alzheimer's disease) are surprisingly all potent HNMT inhibitors, having inhibition constants in the range of 10-100nM. We have determined the structural mode of interaction of these four inhibitors with HNMT. Despite their structural diversity, they all occupy the histamine-binding site, thus blocking access to the enzyme's active site. Near the N terminus of HNMT, several aromatic residues (Phe9, Tyr15, and Phe19) adopt different rotamer conformations or become disordered in the enzyme-inhibitor complexes, accommodating the diverse, rigid hydrophobic groups of the inhibitors. The maximized shape complementarity between the protein aromatic side-chains and aromatic ring(s) of the inhibitors are responsible for the tight binding of these varied inhibitors. Structural basis for inhibition of histamine N-methyltransferase by diverse drugs.,Horton JR, Sawada K, Nishibori M, Cheng X J Mol Biol. 2005 Oct 21;353(2):334-44. PMID:16168438[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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