This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

6i2t

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

CryoEM reconstruction of full-length, fully-glycosylated human butyrylcholinesterase tetramer

6i2t, resolution 5.70Å

Structural highlights

6i2t is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	Cholinesterase, with EC number 3.1.1.8
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CHLE_HUMAN] Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM: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

[CHLE_HUMAN] Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.^[1] ^[2]

Publication Abstract from PubMed

The quaternary structures of the cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are essential for their localization and function. Of practical importance, BChE is a promising therapeutic candidate for intoxication by organophosphate nerve agents and insecticides, and for detoxification of addictive substances. Efficacy of the recombinant enzyme hinges on its having a long circulatory half-life; this, in turn, depends strongly on its ability to tetramerize. Here, we used cryoelectron microscopy (cryo-EM) to determine the structure of the highly glycosylated native BChE tetramer purified from human plasma at 5.7 A. Our structure reveals that the BChE tetramer is organized as a staggered dimer of dimers. Tetramerization is mediated by assembly of the C-terminal tryptophan amphiphilic tetramerization (WAT) helices from each subunit as a superhelical assembly around a central lamellipodin-derived oligopeptide with a proline-rich attachment domain (PRAD) sequence that adopts a polyproline II helical conformation and runs antiparallel. The catalytic domains within a dimer are asymmetrically linked to the WAT/PRAD. In the resulting arrangement, the tetramerization domain is largely shielded by the catalytic domains, which may contribute to the stability of the human BChE (HuBChE) tetramer. Our cryo-EM structure reveals the basis for assembly of the native tetramers and has implications for the therapeutic applications of HuBChE. This mode of tetramerization is seen only in the cholinesterases but may provide a promising template for designing other proteins with improved circulatory residence times.

Cryo-EM structure of the native butyrylcholinesterase tetramer reveals a dimer of dimers stabilized by a superhelical assembly.,Leung MR, van Bezouwen LS, Schopfer LM, Sussman JL, Silman I, Lockridge O, Zeev-Ben-Mordehai T Proc Natl Acad Sci U S A. 2018 Dec 11. pii: 1817009115. doi:, 10.1073/pnas.1817009115. PMID:30538207^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chilukuri N, Duysen EG, Parikh K, diTargiani R, Doctor BP, Lockridge O, Saxena A. Adenovirus-transduced human butyrylcholinesterase in mouse blood functions as a bioscavenger of chemical warfare nerve agents. Mol Pharmacol. 2009 Sep;76(3):612-7. doi: 10.1124/mol.109.055665. Epub 2009 Jun, 19. PMID:19542320 doi:10.1124/mol.109.055665
↑ Amitay M, Shurki A. The structure of G117H mutant of butyrylcholinesterase: nerve agents scavenger. Proteins. 2009 Nov 1;77(2):370-7. doi: 10.1002/prot.22442. PMID:19452557 doi:10.1002/prot.22442
↑ Leung MR, van Bezouwen LS, Schopfer LM, Sussman JL, Silman I, Lockridge O, Zeev-Ben-Mordehai T. Cryo-EM structure of the native butyrylcholinesterase tetramer reveals a dimer of dimers stabilized by a superhelical assembly. Proc Natl Acad Sci U S A. 2018 Dec 11. pii: 1817009115. doi:, 10.1073/pnas.1817009115. PMID:30538207 doi:http://dx.doi.org/10.1073/pnas.1817009115

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6i2t"

@@ Line 3: / Line 3: @@
 <SX load='6i2t' size='340' side='right' viewer='molstar' caption='[[6i2t]], [[Resolution|resolution]] 5.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6i2t]] is a 5 chain structure with 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=6I2T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I2T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6i2t]] is a 5 chain structure with 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=6I2T OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6I2T FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cholinesterase Cholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.8 3.1.1.8] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6i2t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i2t OCA], [http://pdbe.org/6i2t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i2t RCSB], [http://www.ebi.ac.uk/pdbsum/6i2t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i2t ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6i2t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i2t OCA], [http://pdbe.org/6i2t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i2t RCSB], [http://www.ebi.ac.uk/pdbsum/6i2t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i2t ProSAT]</span></td></tr>
 </table>
 == Disease ==

6i2t

From Proteopedia

Current revision

CryoEM reconstruction of full-length, fully-glycosylated human butyrylcholinesterase tetramer

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox