2aow: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 1: Line 1:
[[Image:2aow.gif|left|200px]]
{{Seed}}
[[Image:2aow.png|left|200px]]


<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2aow|  PDB=2aow  |  SCENE=  }}  
{{STRUCTURE_2aow|  PDB=2aow  |  SCENE=  }}  


'''Histamine Methyltransferase (Natural Variant I105) Complexed with the Acetylcholinesterase Inhibitor and Altzheimer's Disease Drug Tacrine'''
===Histamine Methyltransferase (Natural Variant I105) Complexed with the Acetylcholinesterase Inhibitor and Altzheimer's Disease Drug Tacrine===




==Overview==
<!--  
In 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.
The line below this paragraph, {{ABSTRACT_PUBMED_16168438}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 16168438 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_16168438}}


==Disease==
==Disease==
Line 32: Line 36:
[[Category: Classic methyltransferase fold]]
[[Category: Classic methyltransferase fold]]
[[Category: Protein-drug complex]]
[[Category: Protein-drug complex]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 19:18:09 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:50:43 2008''

Revision as of 13:50, 27 July 2008

File:2aow.png

Template:STRUCTURE 2aow

Histamine Methyltransferase (Natural Variant I105) Complexed with the Acetylcholinesterase Inhibitor and Altzheimer's Disease Drug TacrineHistamine Methyltransferase (Natural Variant I105) Complexed with the Acetylcholinesterase Inhibitor and Altzheimer's Disease Drug Tacrine

Template:ABSTRACT PUBMED 16168438

DiseaseDisease

Known disease associated with this structure: Asthma, susceptibility to OMIM:[605238]

About this StructureAbout this Structure

2AOW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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

Page seeded by OCA on Sun Jul 27 13:50:43 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=2aow&oldid=649295"