DB code: S00725

RLCP classification 1.12.30000.14 : Hydrolysis
CATH domain 3.40.50.1820 : Rossmann fold Catalytic domain
E.C. 3.1.1.8
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.1820 : Rossmann fold S00544 S00344 S00517 S00525 S00526 S00720 S00723 S00724 S00919 S00057 S00374 S00345 S00347 S00348 S00346 S00350 S00352 S00353 S00355 S00356 S00358 D00189 D00210 D00539 T00253

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P06276 Cholinesterase
EC 3.1.1.8
Acylcholine acylhydrolase
Choline esterase II
Butyrylcholine esterase
Pseudocholinesterase
NP_000046.1 (Protein)
NM_000055.2 (DNA/RNA sequence)
S09.980 (Serine)
PF08674 (AChE_tetra)
PF00135 (COesterase)
[Graphical View]

KEGG enzyme name
Cholinesterase
Pseudocholinesterase
Butyrylcholine esterase
Non-specific cholinesterase
Choline esterase II (unspecific)
Benzoylcholinesterase
Choline esterase
Butyrylcholinesterase
Propionylcholinesterase
Anticholineesterase
BtChoEase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P06276 CHLE_HUMAN An acylcholine + H(2)O = choline + a carboxylate. Homotetramer, disulfide-linked. Dimer of dimers. Secreted.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C01777 C00001 C00114 C00060 I00084 I00085 I00086
E.C.
Compound acylcholine H2O choline carboxylate Peptidyl-Ser-acylcholine-tetrahedral-intermediate Acyl-enzyme (Peptidyl-Ser-acyl group) Peptidyl-Ser-tetrahedral-intermediate
Type amine group,carbohydrate H2O amine group,carbohydrate carboxyl group
ChEBI 15377
 15377
 		15354
 15354
PubChem 22247451
 962
 22247451
 962
 		305
 305
1p0iA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:BUA
1p0mA00 Unbound Bound:CHT Unbound Unbound Unbound Unbound
1p0pA00 Unbound Analogue:BCH Unbound Unbound Unbound Transition-state-analogue:VXA
1p0qA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:VXA
1xluA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:ISP
1xlvA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:EFS
1xlwA00 Unbound Unbound Unbound Transition-state-analogue:DEP Unbound Unbound
2j4cA00 Unbound Unbound Bound:BUA Unbound Unbound Unbound
2pm8A00 Unbound Unbound Unbound Unbound Unbound Unbound
2pm8B00 Unbound Unbound Unbound Unbound Unbound Unbound
2widA00 Unbound Unbound Unbound Transition-state-analogue:TUN Unbound Unbound
2wifA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:TN6
2wigA00 Unbound Unbound Unbound Transition-state-analogue:TC3 Unbound Unbound
2wijA00 Unbound Unbound Unbound Transition-state-analogue:TN7 Unbound Unbound
2wikA00 Unbound Unbound Unbound Transition-state-analogue:TC5 Unbound Unbound
2wilA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:TCX
2wilB00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:TCX
2wslA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:EFS
2xmbA00 Unbound Unbound Unbound Unbound Unbound Unbound
2xmcA00 Unbound Unbound Unbound Unbound Unbound Unbound
2xmdA00 Unbound Unbound Unbound Transition-state-analogue:DEP Unbound Unbound
2xmgA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:_VX
2xqfA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:_VX
2xqgA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:_VR
2xqiA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:CVX
2xqjA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:_VX
2xqkA00 Unbound Unbound Unbound Transition-state-analogue:_VX Unbound Unbound
2y1kA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:SEP
3djyA00 Unbound Unbound Unbound Transition-state-analogue:SUN Unbound Unbound
3dkkA00 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:SEN
3o9mA00 Unbound Unbound Bound:BEZ Unbound Unbound Unbound
3o9mB00 Unbound Unbound Bound:BEZ Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [1], [5] & Swiss-prot;P06276

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1p0iA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
1p0mA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
1p0pA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
1p0qA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
1xluA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
1xlvA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
1xlwA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2j4cA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2pm8A00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2pm8B00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2widA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2wifA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2wigA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2wijA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2wikA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2wilA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2wilB00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2wslA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2xmbA00 SER 198;GLU 325;HIS 438 GLY 116;;ALA 199 mutant G117H
2xmcA00 SER 198;GLU 325;HIS 438 GLY 116;;ALA 199 mutant G117H
2xmdA00 SER 198;GLU 325;HIS 438 GLY 116;;ALA 199 mutant G117H
2xmgA00 SER 198;GLU 325;HIS 438 GLY 116;;ALA 199 mutant G117H
2xqfA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2xqgA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2xqiA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2xqjA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2xqkA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
2y1kA00 ;GLU 325;HIS 438 SEP 198 GLY 116;GLY 117;ALA 199 Phosphorylated S198
3djyA00 ;GLU 325;HIS 438 SUN 198 GLY 116;GLY 117;ALA 199 S198-Tabun
3dkkA00 ;GLU 325;HIS 438 SEN 198 GLY 116;GLY 117;ALA 199 S198-Tabun
3o9mA00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199
3o9mB00 SER 198;GLU 325;HIS 438 GLY 116;GLY 117;ALA 199

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Scheme 1
[3]
p.41145-41146
[5]
Figure 4

References
[1]
Resource
Comments
Medline ID
PubMed ID 11123949
Journal Biochemistry
Year 2000
Volume 39
Pages 16200-5
Authors Viragh C, Harris TK, Reddy PM, Massiah MA, Mildvan AS, Kovach IM
Title NMR evidence for a short, strong hydrogen bond at the active site of a cholinesterase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 12603134
Journal J Am Chem Soc
Year 2003
Volume 125
Pages 2462-74
Authors Zhan CG, Zheng F, Landry DW
Title Fundamental reaction mechanism for cocaine hydrolysis in human butyrylcholinesterase.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 29-557 IN COMPLEX WITH SUBSTRATE, SUBUNIT, GLYCOSYLATION AT ASN-85; ASN-134; ASN-269; ASN-369 AND ASN-513, DISULFIDE BONDS, ACTIVE SITE.
Medline ID
PubMed ID 12869558
Journal J Biol Chem
Year 2003
Volume 278
Pages 41141-7
Authors Nicolet Y, Lockridge O, Masson P, Fontecilla-Camps JC, Nachon F
Title Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products.
Related PDB 1p0i 1p0m 1p0p 1p0q
Related UniProtKB P06276
[4]
Resource
Comments
Medline ID
PubMed ID 15128307
Journal Eur J Biochem
Year 2004
Volume 271
Pages 1980-90
Authors Masson P, Bec N, Froment MT, Nachon F, Balny C, Lockridge O, Schopfer LM
Title Rate-determining step of butyrylcholinesterase-catalyzed hydrolysis of benzoylcholine and benzoylthiocholine. Volumetric study of wild-type and D70G mutant behavior.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 29-557 IN COMPLEX WITH ECHOTHIOPHATE, DISULFIDE BONDS, GLYCOSYLATION AT ASN-85; ASN-134; ASN-269; ASN-369 AND ASN-513.
Medline ID
PubMed ID 15667209
Journal Biochemistry
Year 2005
Volume 44
Pages 1154-62
Authors Nachon F, Asojo OA, Borgstahl GE, Masson P, Lockridge O
Title Role of water in aging of human butyrylcholinesterase inhibited by echothiophate: the crystal structure suggests two alternative mechanisms of aging.
Related PDB 1xlu 1xlv 1xlw
Related UniProtKB P06276
[6]
Resource
Comments
Medline ID
PubMed ID 16768449
Journal Biochemistry
Year 2006
Volume 45
Pages 7529-43
Authors Suarez D, Diaz N, Fontecilla-Camps J, Field MJ
Title A computational study of the deacylation mechanism of human butyrylcholinesterase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 16288482
Journal Proteins
Year 2006
Volume 62
Pages 99-110
Authors Gao D, Zhan CG
Title Modeling evolution of hydrogen bonding and stabilization of transition states in the process of cocaine hydrolysis catalyzed by human butyrylcholinesterase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 17768338
Journal Acta Crystallogr Sect F Struct Biol Cryst Commun
Year 2007
Volume 63
Pages 723-7
Authors Ngamelue MN, Homma K, Lockridge O, Asojo OA
Title Crystallization and X-ray structure of full-length recombinant human butyrylcholinesterase.
Related PDB 2pm8
Related UniProtKB P06276
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS), DISULFIDE BONDS, GLYCOSYLATION AT ASN-85; ASN-134; ASN-369 AND ASN-513, SUBUNIT.
Medline ID
PubMed ID 17355286
Journal FEBS J
Year 2007
Volume 274
Pages 1849-61
Authors Frasco MF, Colletier JP, Weik M, Carvalho F, Guilhermino L, Stojan J, Fournier D
Title Mechanisms of cholinesterase inhibition by inorganic mercury.
Related PDB 2j4c
Related UniProtKB P06276
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 29-557 IN COMPLEX WITH TABUN, ENZYME REGULATION, MASS SPECTROMETRY, GLYCOSYLATION AT ASN-85; ASN-134; ASN-284; ASN-369 AND ASN-513.
Medline ID
PubMed ID 18975951
Journal J Am Chem Soc
Year 2008
Volume 130
Pages 16011-20
Authors Carletti E, Li H, Li B, Ekstrom F, Nicolet Y, Loiodice M, Gillon E, Froment MT, Lockridge O, Schopfer LM, Masson P, Nachon F
Title Aging of cholinesterases phosphylated by tabun proceeds through O-dealkylation.
Related PDB 3djy 3dkk
Related UniProtKB P06276
[11]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 29-557 IN COMPLEX WITH TABUN ANALOGS, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION AT ASN-85; ASN-134; ASN-269; ASN-284; ASN-369 AND ASN-513, ENZYME REGULATION.
Medline ID
PubMed ID 19368529
Journal Biochem J
Year 2009
Volume 421
Pages 97-106
Authors Carletti E, Aurbek N, Gillon E, Loiodice M, Nicolet Y, Fontecilla-Camps JC, Masson P, Thiermann H, Nachon F, Worek F
Title Structure-activity analysis of aging and reactivation of human butyrylcholinesterase inhibited by analogues of tabun.
Related PDB 2wid 2wif 2wig 2wij 2wik 2wil 2wsl
Related UniProtKB P06276
[12]
Resource
Comments
Medline ID
PubMed ID 19508180
Journal Protein Pept Lett
Year 2009
Volume 16
Pages 1215-24
Authors Masson P, Carletti E, Nachon F
Title Structure, activities and biomedical applications of human butyrylcholinesterase.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 21091433
Journal Biochem J
Year 2010
Volume 434
Pages 73-82
Authors Nachon F, Carletti E, Wandhammer M, Nicolet Y, Schopfer LM, Masson P, Lockridge O
Title X-ray crystallographic snapshots of reaction intermediates in the G117H mutant of human butyrylcholinesterase, a nerve agent target engineered into a catalytic bioscavenger.
Related PDB 2xmb 2xmc 2xmd 2xmg
Related UniProtKB P06276
[14]
Resource
Comments
Medline ID
PubMed ID 20399202
Journal Chem Biol Interact
Year 2010
Volume 187
Pages 241-5
Authors Vyas S, Beck JM, Xia S, Zhang J, Hadad CM
Title Butyrylcholinesterase and G116H, G116S, G117H, G117N, E197Q and G117H/E197Q mutants: a molecular dynamics study.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 20493178
Journal Chem Biol Interact
Year 2010
Volume 187
Pages 124-7
Authors Wiley KL, Tormos JR, Quinn DM
Title A secondary isotope effect study of equine serum butyrylcholinesterase-catalyzed hydrolysis of acetylthiocholine.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 21454498
Journal J Biol Chem
Year 2011
Volume 286
Pages 16783-9
Authors Wandhammer M, Carletti E, Van der Schans M, Gillon E, Nicolet Y, Masson P, Goeldner M, Noort D, Nachon F
Title Structural study of the complex stereoselectivity of human butyrylcholinesterase for the neurotoxic V-agents.
Related PDB 2xqf 2xqg 2xqi 2xqj 2xqk
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 21438623
Journal Chem Res Toxicol
Year 2011
Volume 24
Pages 797-808
Authors Carletti E, Schopfer LM, Colletier JP, Froment MT, Nachon F, Weik M, Lockridge O, Masson P
Title Reaction of cresyl saligenin phosphate, the organophosphorus agent implicated in aerotoxic syndrome, with human cholinesterases: mechanistic studies employing kinetics, mass spectrometry, and X-ray structure analysis.
Related PDB 2y1k
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 21505234
Journal Acta Crystallogr Sect F Struct Biol Cryst Commun
Year 2011
Volume 67
Pages 434-7
Authors Asojo OA, Asojo OA, Ngamelue MN, Homma K, Lockridge O
Title Cocrystallization studies of full-length recombinant butyrylcholinesterase (BChE) with cocaine.
Related PDB 3o9m
Related UniProtKB

Comments
This enzyme belongs to alpha/beta-hydrolase superfamily, and is closely related to acetylcholinesterase (EC 3.1.1.7; S00057 in EzCatDB).
As this enzyme has got the same catalytic site as that of acetylcholinesterase (S00057), it seems to catalyze the same reaction mechanism as the homologous enzyme.
Moreover, since this enzyme can hydrolyze or scavenge a wide range of toxic esters, including heroin, cocain, several types of pesticides, and nerve agent, such as sarin and VX, it is thought toxicologically important (see [2], [5], [7], [10], [12], [13], [16], [18]).

Created Updated
2011-02-02 2012-02-22