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[[Image:1jqe.gif|left|200px]]


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==Crystal Structure Analysis of Human Histamine Methyltransferase (Ile105 Polymorphic Variant) Complexed with AdoHcy and Antimalarial Drug Quinacrine==
The line below this paragraph, containing "STRUCTURE_1jqe", creates the "Structure Box" on the page.
<StructureSection load='1jqe' size='340' side='right'caption='[[1jqe]], [[Resolution|resolution]] 1.91&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'>[[1jqe]] 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=1JQE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JQE 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]] 1.91&#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=QUN:QUINACRINE'>QUN</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
{{STRUCTURE_1jqe|  PDB=1jqe  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jqe OCA], [https://pdbe.org/1jqe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jqe RCSB], [https://www.ebi.ac.uk/pdbsum/1jqe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jqe ProSAT]</span></td></tr>
 
</table>
'''Crystal Structure Analysis of Human Histamine Methyltransferase (Ile105 Polymorphic Variant) Complexed with AdoHcy and Antimalarial Drug Quinacrine'''
== Function ==
 
[https://www.uniprot.org/uniprot/HNMT_HUMAN HNMT_HUMAN] Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.
 
== Evolutionary Conservation ==
==Overview==
[[Image:Consurf_key_small.gif|200px|right]]
BACKGROUND: Histamine plays important biological roles in cell-to-cell communication; it is a mediator in allergic responses, a regulator of gastric acid secretion, a messenger in bronchial asthma, and a neurotransmitter in the central nervous system. Histamine acts by binding to histamine receptors, and its local action is terminated primarily by methylation. Human histamine N-methyltransferase (HNMT) has a common polymorphism at residue 105 that correlates with the high- (Thr) and low- (Ile) activity phenotypes. RESULTS: Two ternary structures of human HNMT have been determined: the Thr105 variant complexed with its substrate histamine and reaction product AdoHcy and the Ile105 variant complexed with an inhibitor (quinacrine) and AdoHcy. Our steady-state kinetic data indicate that the recombinant Ile105 variant shows 1.8- and 1.3-fold increases in the apparent K(M) for AdoMet and histamine, respectively, and slightly (16%) but consistently lower specific activity as compared to that of the Thr105 variant. These differences hold over a temperature range of 25 degrees C-45 degrees C in vitro. Only at a temperature of 50 degrees C or higher is the Ile105 variant more thermolabile than the Thr105 enzyme. CONCLUSIONS: HNMT has a 2 domain structure including a consensus AdoMet binding domain, where the residue 105 is located on the surface, consistent with the kinetic data that the polymorphism does not affect overall protein stability at physiological temperatures but lowers K(M) values for AdoMet and histamine. The interactions between HNMT and quinacrine provide the first structural insights into a large group of pharmacologic HNMT inhibitors and their mechanisms of inhibition.
Check<jmol>
 
  <jmolCheckbox>
==Disease==
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jq/1jqe_consurf.spt"</scriptWhenChecked>
Known disease associated with this structure: Asthma, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605238 605238]]
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 
    <text>to colour the structure by Evolutionary Conservation</text>
==About this Structure==
  </jmolCheckbox>
1JQE 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=1JQE OCA].  
</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=1jqe ConSurf].
 
<div style="clear:both"></div>
==Reference==
__TOC__
Two polymorphic forms of human histamine methyltransferase: structural, thermal, and kinetic comparisons., Horton JR, Sawada K, Nishibori M, Zhang X, Cheng X, Structure. 2001 Sep;9(9):837-49. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11566133 11566133]
</StructureSection>
[[Category: Histamine N-methyltransferase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Cheng, X.]]
[[Category: Cheng X]]
[[Category: Horton, J R.]]
[[Category: Horton JR]]
[[Category: Nishibori, M.]]
[[Category: Nishibori M]]
[[Category: Sawada, K.]]
[[Category: Sawada K]]
[[Category: Zhang, X.]]
[[Category: Zhang X]]
[[Category: Classic methyltransferase fold]]
[[Category: Polymorphic variant]]
[[Category: Protein-substrate-cofactor complex]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 21:38:27 2008''

Latest revision as of 10:41, 7 February 2024

Crystal Structure Analysis of Human Histamine Methyltransferase (Ile105 Polymorphic Variant) Complexed with AdoHcy and Antimalarial Drug QuinacrineCrystal Structure Analysis of Human Histamine Methyltransferase (Ile105 Polymorphic Variant) Complexed with AdoHcy and Antimalarial Drug Quinacrine

Structural highlights

1jqe is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.91Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

1jqe, resolution 1.91Å

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