Butyrylcholinesterase: Difference between revisions

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Joel L. Sussman, David Canner, Alexander Berchansky, Jaime Prilusky, Michal Harel, Lakshmi Venkatachalam

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-<StructureSection load='1p0i' size='350' side='right' caption='Structure of human BAG-1 BAG domain (green) complex with HSC70 ATPase domain (grey) and ATP (PDB entry [[1p0i]])' scene=''>
+<StructureSection load='1p0m' size='350' side='right' scene='39/399020/Cv/3' caption='Glycosylated human butyrylcholinesterase complex with choline, glycerol, sulfate and Cl- ions (PDB code [[1p0m]])'>
-{{STRUCTURE_4aqd|  PDB=2xmb  | SIZE=400| SCENE= |right|CAPTION=Glycosylated human butyrylcholinesterase complex with sulfate, glycerol, Cl- (green) and Na+ (purple) ions [[4aqd]] }}
+__TOC__
+== Function ==
-[[Image:HuBChE.png|left|300px]]
+[[Butyrylcholinesterase]] (BChE) is an enzyme widely distributed throughout the body in humans, but particularly prevalent in serum, where it occurs as a tetramer of catalytic subunits. It is distinguished from the homologous enzyme, acetylcholinesterase, by its ability to hydrolyze the non-natural substrate butyrylcholine as well as the neurotransmitter, acetylcholine. <ref>PMID:12563284</ref>
-{{STRUCTURE_2pm8|  PDB=2pm8  | SIZE=300| SCENE=Butyrylcholinesterase/Cv/1 |right|CAPTION=Recombinant full length human butyrylcholinesterase [[2pm8]] }}
-[[Butyrylcholinesterase]] (BChE) is an enzyme widely distributed throughout the body in humans, but particularly prevalent in serum, where it occurs as a tetramer of catalytic subunits. It is distinguished from the homologous enzyme, acetylcholinesterase, by its ability to hydrolyze the non-natural substrate butyrylcholine as well as the neurotransmitter, acetylcholine. Its biological role remains obscure, but mutations in the human BCHE gene result in prolonged post-surgical apnea due to the inability of the mutant BChEs to hydrolyse the local anaesthetic, succinylcholine. BChE finds medical use as a bioscavenger for overcoming organophosphate (OP) nerve agent and insecticide intoxication by interacting rapidly with the toxic agents. Crystal structures of both the native enzyme and of its conjugates with nerve agents are available. The image at the right correspond to one representative BChE, ''i.e.'' the crystal structure of recombinant full length human butyrylcholinesterase ([[2pm8]]).
-===3D structures of BChE===
+== Relevance ==
-Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
+BChE finds medical use as a bioscavenger for overcoming organophosphate (OP) nerve agent and insecticide intoxication by interacting rapidly with the toxic agents.
-== hBChE - Apo human ==
+== Disease ==
-[[2pm8]], [[1p0i]] - hBChE - human  <br />
+BChE biological role remains obscure, but mutations in the human BCHE gene result in prolonged post-surgical apnea due to the inability of the mutant BChEs to hydrolyse the local anaesthetic, succinylcholine.
-[[2xmb]] – hBChE (mutant)+SO4<br />
-[[2xmc]] - hBChE (mutant)+F <br />
-[[4aqd]] - hBChE (fully glycosylated)
-== BChE+OP irreversible inhibitors, including nerve agents and insecticides ==
+== Structural highlights ==
-[[3djy]], [[3dkk]] - hBChE+tabun <br />
+Like in the AChE structure, BChE active site is located at the bottom of a ca. 20A deep gorge. The <scene name='39/399020/Cv/6'>active site of BChE</scene> is similar to that of AChE. <ref>PMID:12869558</ref> Water molecule is shown as red sphere. The differences are noticed in the lining of the gorge were some of the aromatic residues in AChE are substituted by hydrophobic ones and in the active site acyl-binding pocket where 2 Phe residues are replaced by Leu and Val in BChE.
-[[2wid]], [[2wif]] - hBChE+Tabun analogue TA1 <br />
-[[2wsl]], [[2wig]] – hBChE+Tabun analogue TA4 <br />
-[[2wil]], [[2wij]] - hBChE+Tabun analogue TA5 <br />
-[[2wik]] - hBChE+Tabun analogue TA6 <br />
-[[1xlw]] - hBChE+echothiophate <br />
-[[1xmd]], [[2xmd]] – hBChE (mutant)+echothiophate<br />
-[[1p0q]] - hBChE+soman <br />
-[[1xlu]] - hBChE+Di-Isopropyl-Phosphoro-Fluoridate (DFP)<br />
-[[2xmg]] - hBChE (mutant)+VX<br />
-[[1xlv]] – hBChE+ethyl dihydrogen phosphate<br />
-[[2y1k]], [[4bbz]] - hBChE (mutant) + CBDP <br />
-[[4b0p]], [[4b0o]] - hBChE (Aged) + pyridinium derivative<br />
-[[4axb]] – hBChE (aged) + 2-PAM
-== BChE+inhibitor binding at surface of the protein (far from the active site) ==
+==3D structures of BChE==
+[[Butyrylcholinesterase 3D structures]]
-[[2j4c]] – hBChE+ HgCl2 <br />
+</StructureSection>
-== BChE + substrate analogues mimicking the binding of the substrate butyrylcholine ==
-[[1p0m]] - hBChE+choline <br />
-[[1p0p]] - hBChE+butyrylthiocholine<br />
-[[3o9m]] - hBChE + benzoic acid<br />
-[[1eho]], [[1ehq]], [[1kcj]] – hBChE + cocaine - model<br />
-[[4bds]] – hBChE + tacrine<br />
 ==Additional Resources==
 For additional information, see: [[Alzheimer's Disease]]
 <br />
+== References ==
+<references/>
 [[Category:Topic Page]]