EzCatDB: S00725
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DB codeS00725
RLCP classification1.12.30000.14 : Hydrolysis
CATH domainDomain 13.40.50.1820 : Rossmann foldCatalytic domain
E.C.3.1.1.8

CATH domainRelated DB codes (homologues)
3.40.50.1820 : Rossmann foldS00544,S00344,S00517,S00525,S00526,S00720,S00723,S00724,S00919,S00057,S00374,S00345,S00347,S00348,S00346,S00350,S00352,S00353,S00355,S00356,S00358,D00189,D00210,D00539,T00253

Enzyme Name
UniProtKBKEGG

P06276
Protein nameCholinesteraseCholinesterase
Pseudocholinesterase
Butyrylcholine esterase
Non-specific cholinesterase
Choline esterase II (unspecific)
Benzoylcholinesterase
Choline esterase
Butyrylcholinesterase
Propionylcholinesterase
Anticholineesterase
BtChoEase
SynonymsEC 3.1.1.8
Acylcholine acylhydrolase
Choline esterase II
Butyrylcholine esterase
Pseudocholinesterase
RefSeqNP_000046.1 (Protein)
NM_000055.2 (DNA/RNA sequence)
MEROPSS09.980 (Serine)
PfamPF08674 (AChE_tetra)
PF00135 (COesterase)
[Graphical view]


UniProtKB:Accession NumberP06276
Entry nameCHLE_HUMAN
ActivityAn acylcholine + H(2)O = choline + a carboxylate.
SubunitHomotetramer, disulfide-linked. Dimer of dimers.
Subcellular locationSecreted.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC01777C00001C00114C00060I00084I00085I00086
CompoundacylcholineH2OcholinecarboxylatePeptidyl-Ser-acylcholine-tetrahedral-intermediateAcyl-enzyme (Peptidyl-Ser-acyl group)Peptidyl-Ser-tetrahedral-intermediate
Typeamine group,carbohydrateH2Oamine group,carbohydratecarboxyl group


ChEBI
15377
15354




PubChem
962
22247451
305




               
1p0iA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:BUA
1p0mA00Unbound Bound:CHTUnboundUnboundUnboundUnbound
1p0pA00Unbound Analogue:BCHUnboundUnboundUnboundTransition-state-analogue:VXA
1p0qA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:VXA
1xluA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:ISP
1xlvA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:EFS
1xlwA00Unbound UnboundUnboundTransition-state-analogue:DEPUnboundUnbound
2j4cA00Unbound UnboundBound:BUAUnboundUnboundUnbound
2pm8A00Unbound UnboundUnboundUnboundUnboundUnbound
2pm8B00Unbound UnboundUnboundUnboundUnboundUnbound
2widA00Unbound UnboundUnboundTransition-state-analogue:TUNUnboundUnbound
2wifA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:TN6
2wigA00Unbound UnboundUnboundTransition-state-analogue:TC3UnboundUnbound
2wijA00Unbound UnboundUnboundTransition-state-analogue:TN7UnboundUnbound
2wikA00Unbound UnboundUnboundTransition-state-analogue:TC5UnboundUnbound
2wilA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:TCX
2wilB00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:TCX
2wslA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:EFS
2xmbA00Unbound UnboundUnboundUnboundUnboundUnbound
2xmcA00Unbound UnboundUnboundUnboundUnboundUnbound
2xmdA00Unbound UnboundUnboundTransition-state-analogue:DEPUnboundUnbound
2xmgA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:_VX
2xqfA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:_VX
2xqgA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:_VR
2xqiA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:CVX
2xqjA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:_VX
2xqkA00Unbound UnboundUnboundTransition-state-analogue:_VXUnboundUnbound
2y1kA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:SEP
3djyA00Unbound UnboundUnboundTransition-state-analogue:SUNUnboundUnbound
3dkkA00Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:SEN
3o9mA00Unbound UnboundBound:BEZUnboundUnboundUnbound
3o9mB00Unbound UnboundBound:BEZUnboundUnboundUnbound

Active-site residues
resource
Literature [1], [5] & Swiss-prot;P06276
pdbCatalytic residuesModified residuesMain-chain involved in catalysiscomment
            
1p0iA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
1p0mA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
1p0pA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
1p0qA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
1xluA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
1xlvA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
1xlwA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2j4cA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2pm8A00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2pm8B00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2widA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2wifA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2wigA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2wijA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2wikA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2wilA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2wilB00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2wslA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2xmbA00SER 198;GLU 325;HIS 438
       
GLY 116;       ;ALA 199
mutant G117H
2xmcA00SER 198;GLU 325;HIS 438
       
GLY 116;       ;ALA 199
mutant G117H
2xmdA00SER 198;GLU 325;HIS 438
       
GLY 116;       ;ALA 199
mutant G117H
2xmgA00SER 198;GLU 325;HIS 438
       
GLY 116;       ;ALA 199
mutant G117H
2xqfA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2xqgA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2xqiA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2xqjA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
2xqkA00SER 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
3o9mA00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 
3o9mB00SER 198;GLU 325;HIS 438
       
GLY 116;GLY 117;ALA 199
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Scheme 1
[3]p.41145-41146
[5]Figure 4

references
[1]
PubMed ID11123949
JournalBiochemistry
Year2000
Volume39
Pages16200-5
AuthorsViragh C, Harris TK, Reddy PM, Massiah MA, Mildvan AS, Kovach IM
TitleNMR evidence for a short, strong hydrogen bond at the active site of a cholinesterase.
[2]
PubMed ID12603134
JournalJ Am Chem Soc
Year2003
Volume125
Pages2462-74
AuthorsZhan CG, Zheng F, Landry DW
TitleFundamental reaction mechanism for cocaine hydrolysis in human butyrylcholinesterase.
[3]
CommentsX-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.
PubMed ID12869558
JournalJ Biol Chem
Year2003
Volume278
Pages41141-7
AuthorsNicolet Y, Lockridge O, Masson P, Fontecilla-Camps JC, Nachon F
TitleCrystal structure of human butyrylcholinesterase and of its complexes with substrate and products.
Related PDB1p0i,1p0m,1p0p,1p0q
Related UniProtKBP06276
[4]
PubMed ID15128307
JournalEur J Biochem
Year2004
Volume271
Pages1980-90
AuthorsMasson P, Bec N, Froment MT, Nachon F, Balny C, Lockridge O, Schopfer LM
TitleRate-determining step of butyrylcholinesterase-catalyzed hydrolysis of benzoylcholine and benzoylthiocholine. Volumetric study of wild-type and D70G mutant behavior.
[5]
CommentsX-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.
PubMed ID15667209
JournalBiochemistry
Year2005
Volume44
Pages1154-62
AuthorsNachon F, Asojo OA, Borgstahl GE, Masson P, Lockridge O
TitleRole of water in aging of human butyrylcholinesterase inhibited by echothiophate: the crystal structure suggests two alternative mechanisms of aging.
Related PDB1xlu,1xlv,1xlw
Related UniProtKBP06276
[6]
PubMed ID16768449
JournalBiochemistry
Year2006
Volume45
Pages7529-43
AuthorsSuarez D, Diaz N, Fontecilla-Camps J, Field MJ
TitleA computational study of the deacylation mechanism of human butyrylcholinesterase.
[7]
PubMed ID16288482
JournalProteins
Year2006
Volume62
Pages99-110
AuthorsGao D, Zhan CG
TitleModeling evolution of hydrogen bonding and stabilization of transition states in the process of cocaine hydrolysis catalyzed by human butyrylcholinesterase.
[8]
PubMed ID17768338
JournalActa Crystallogr Sect F Struct Biol Cryst Commun
Year2007
Volume63
Pages723-7
AuthorsNgamelue MN, Homma K, Lockridge O, Asojo OA
TitleCrystallization and X-ray structure of full-length recombinant human butyrylcholinesterase.
Related PDB2pm8
Related UniProtKBP06276
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS), DISULFIDE BONDS, GLYCOSYLATION AT ASN-85; ASN-134; ASN-369 AND ASN-513, SUBUNIT.
PubMed ID17355286
JournalFEBS J
Year2007
Volume274
Pages1849-61
AuthorsFrasco MF, Colletier JP, Weik M, Carvalho F, Guilhermino L, Stojan J, Fournier D
TitleMechanisms of cholinesterase inhibition by inorganic mercury.
Related PDB2j4c
Related UniProtKBP06276
[10]
CommentsX-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.
PubMed ID18975951
JournalJ Am Chem Soc
Year2008
Volume130
Pages16011-20
AuthorsCarletti E, Li H, Li B, Ekstrom F, Nicolet Y, Loiodice M, Gillon E, Froment MT, Lockridge O, Schopfer LM, Masson P, Nachon F
TitleAging of cholinesterases phosphylated by tabun proceeds through O-dealkylation.
Related PDB3djy,3dkk
Related UniProtKBP06276
[11]
CommentsX-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.
PubMed ID19368529
JournalBiochem J
Year2009
Volume421
Pages97-106
AuthorsCarletti E, Aurbek N, Gillon E, Loiodice M, Nicolet Y, Fontecilla-Camps JC, Masson P, Thiermann H, Nachon F, Worek F
TitleStructure-activity analysis of aging and reactivation of human butyrylcholinesterase inhibited by analogues of tabun.
Related PDB2wid,2wif,2wig,2wij,2wik,2wil,2wsl
Related UniProtKBP06276
[12]
PubMed ID19508180
JournalProtein Pept Lett
Year2009
Volume16
Pages1215-24
AuthorsMasson P, Carletti E, Nachon F
TitleStructure, activities and biomedical applications of human butyrylcholinesterase.
[13]
PubMed ID21091433
JournalBiochem J
Year2010
Volume434
Pages73-82
AuthorsNachon F, Carletti E, Wandhammer M, Nicolet Y, Schopfer LM, Masson P, Lockridge O
TitleX-ray crystallographic snapshots of reaction intermediates in the G117H mutant of human butyrylcholinesterase, a nerve agent target engineered into a catalytic bioscavenger.
Related PDB2xmb,2xmc,2xmd,2xmg
Related UniProtKBP06276
[14]
PubMed ID20399202
JournalChem Biol Interact
Year2010
Volume187
Pages241-5
AuthorsVyas S, Beck JM, Xia S, Zhang J, Hadad CM
TitleButyrylcholinesterase and G116H, G116S, G117H, G117N, E197Q and G117H/E197Q mutants: a molecular dynamics study.
[15]
PubMed ID20493178
JournalChem Biol Interact
Year2010
Volume187
Pages124-7
AuthorsWiley KL, Tormos JR, Quinn DM
TitleA secondary isotope effect study of equine serum butyrylcholinesterase-catalyzed hydrolysis of acetylthiocholine.
[16]
PubMed ID21454498
JournalJ Biol Chem
Year2011
Volume286
Pages16783-9
AuthorsWandhammer M, Carletti E, Van der Schans M, Gillon E, Nicolet Y, Masson P, Goeldner M, Noort D, Nachon F
TitleStructural study of the complex stereoselectivity of human butyrylcholinesterase for the neurotoxic V-agents.
Related PDB2xqf,2xqg,2xqi,2xqj,2xqk
[17]
PubMed ID21438623
JournalChem Res Toxicol
Year2011
Volume24
Pages797-808
AuthorsCarletti E, Schopfer LM, Colletier JP, Froment MT, Nachon F, Weik M, Lockridge O, Masson P
TitleReaction 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 PDB2y1k
[18]
PubMed ID21505234
JournalActa Crystallogr Sect F Struct Biol Cryst Commun
Year2011
Volume67
Pages434-7
AuthorsAsojo OA, Asojo OA, Ngamelue MN, Homma K, Lockridge O
TitleCocrystallization studies of full-length recombinant butyrylcholinesterase (BChE) with cocaine.
Related PDB3o9m

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]).

createdupdated
2011-02-022012-02-22


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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