View source for 3rze


==Structure of the human histamine H1 receptor in complex with doxepin==
<StructureSection load='3rze' size='340' side='right'caption='[[3rze]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3rze]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RZE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RZE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5EH:(3E)-3-(DIBENZO[B,E]OXEPIN-11(6H)-YLIDENE)-N,N-DIMETHYLPROPAN-1-AMINE'>5EH</scene>, <scene name='pdbligand=D7V:(3Z)-3-(DIBENZO[B,E]OXEPIN-11(6H)-YLIDENE)-N,N-DIMETHYLPROPAN-1-AMINE'>D7V</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=3rze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rze OCA], [https://pdbe.org/3rze PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rze RCSB], [https://www.ebi.ac.uk/pdbsum/3rze PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rze ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HRH1_HUMAN HRH1_HUMAN] In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.[https://www.uniprot.org/uniprot/ENLYS_BPT4 ENLYS_BPT4] Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.<ref>PMID:22389108</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The biogenic amine histamine is an important pharmacological mediator involved in pathophysiological processes such as allergies and inflammations. Histamine H(1) receptor (H(1)R) antagonists are very effective drugs alleviating the symptoms of allergic reactions. Here we show the crystal structure of the H(1)R complex with doxepin, a first-generation H(1)R antagonist. Doxepin sits deep in the ligand-binding pocket and directly interacts with Trp 428(6.48), a highly conserved key residue in G-protein-coupled-receptor activation. This well-conserved pocket with mostly hydrophobic nature contributes to the low selectivity of the first-generation compounds. The pocket is associated with an anion-binding region occupied by a phosphate ion. Docking of various second-generation H(1)R antagonists reveals that the unique carboxyl group present in this class of compounds interacts with Lys 191(5.39) and/or Lys 179(ECL2), both of which form part of the anion-binding region. This region is not conserved in other aminergic receptors, demonstrating how minor differences in receptors lead to pronounced selectivity differences with small molecules. Our study sheds light on the molecular basis of H(1)R antagonist specificity against H(1)R.

Structure of the human histamine H1 receptor complex with doxepin.,Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S Nature. 2011 Jun 22;475(7354):65-70. doi: 10.1038/nature10236. PMID:21697825<ref>PMID:21697825</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3rze" style="background-color:#fffaf0;"></div>

==See Also==
*[[G protein-coupled receptor|G protein-coupled receptor]]
*[[Lysozyme 3D structures|Lysozyme 3D structures]]
*[[Neurotransmitters|Neurotransmitters]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia virus T4]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Abagyan R]]
[[Category: Cherezov V]]
[[Category: Han GW]]
[[Category: Iwata S]]
[[Category: Katritch V]]
[[Category: Kobayashi T]]
[[Category: Liu W]]
[[Category: Shimamura T]]
[[Category: Shiroishi M]]
[[Category: Stevens R]]
[[Category: Tsujimoto H]]
[[Category: Weyand S]]
[[Category: Winter G]]