View source for 4bds


==Human butyrylcholinesterase in complex with tacrine==
<StructureSection load='4bds' size='340' side='right'caption='[[4bds]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4bds]] is a 1 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=4BDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BDS 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FPK:1-FORMYL-L-PROLINE'>FPK</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=THA:TACRINE'>THA</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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=4bds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bds OCA], [https://pdbe.org/4bds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bds RCSB], [https://www.ebi.ac.uk/pdbsum/4bds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bds ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN] Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM:[https://omim.org/entry/177400 177400]. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency. BChE deficiency is a multifactorial disorder. The hereditary condition is transmitted as an autosomal recessive trait.
== Function ==
[https://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN] Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.<ref>PMID:19542320</ref> <ref>PMID:19452557</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The multifunctional nature of Alzheimer's disease calls for multi-target directed ligands (MTDLs) able to act on different components of the pathology, like the cholinergic dysfunction and amyloid aggregation. Such MTDLs are usually based on cholinesterase inhibitors (e.g., tacrine or huprine) coupled to another active molecule aimed at a different target. To aid in the design of these MTDLs we report the crystal structures of human acetylcholinesterase (hAChE) in complex with FAS-2 and a hydroxylated derivative of huprine (huprine W), and of human butyrylcholinesterase (hBChE) in complex with tacrine. Huprine W in hAChE and tacrine in hBChE reside in strikingly similar positions highlighting the conservation of key interactions, namely, pi-pi/cation-pi interactions with Trp86(82), and hydrogen bonding with the main chain carbonyl of the catalytic histidine. Huprine W forms additional interactions with hAChE which explains its superior affinity: the isoquinoline moiety is associated with a group of aromatic residues (Tyr337, Phe338 and Phe295 not present in hBChE) in addition to Trp86; the hydroxyl group is hydrogen bonded to both the catalytic serine and residues in the oxyanion hole; and the chlorine substituent is nested in a hydrophobic pocket interacting strongly with Trp439. There is no pocket in hBChE able to accommodate the chlorine substituent.

Crystal Structures of Human Cholinesterases in Complex with Huprine W and Tacrine: Elements of Specificity for Anti-Alzheimer's Drugs Targeting Acetyl- and Butyrylcholinesterase.,Nachon F, Carletti E, Ronco C, Trovaslet M, Nicolet Y, Jean L, Renard PY Biochem J. 2013 May 17. PMID:23679855<ref>PMID:23679855</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4bds" style="background-color:#fffaf0;"></div>

==See Also==
*[[Butyrylcholinesterase 3D structures|Butyrylcholinesterase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Carletti E]]
[[Category: Jean L]]
[[Category: Nachon F]]
[[Category: Nicolet Y]]
[[Category: Renard P-Y]]
[[Category: Ronco C]]
[[Category: Trovaslet M]]