EzCatDB: S00057

DB codeS00057
RLCP classification1.12.30000.14
CATH domainDomain 13.40.50.1820Catalytic domain
E.C.3.1.1.7
CSA2ace

CATH domainRelated DB codes (homologues)
3.40.50.1820S00544,S00344,S00517,S00525,S00526,S00720,S00723,S00724,S00725,S00919,S00374,S00345,S00347,S00348,S00346,S00350,S00352,S00353,S00355,S00356,S00358,D00189,D00210,D00539,T00253

Enzyme Name
Swiss-protKEGG

P04058P22303
Protein nameAcetylcholinesteraseAcetylcholinesteraseacetylcholinesterase
true cholinesterase
choline esterase I
cholinesterase
acetylthiocholinesterase
acetylcholine hydrolase
acetyl.beta-methylcholinesterase
AcCholE
SynonymsAChE
EC 3.1.1.7
AChE
EC 3.1.1.7

KEGG pathways
MAP codePathways
MAP00564Glycerophospholipid metabolism

Swiss-prot:Accession NumberP04058P22303
Entry nameACES_TORCAACES_HUMAN
ActivityAcetylcholine + H(2)O = choline + acetate.Acetylcholine + H(2)O = choline + acetate.
SubunitIsoform H form is an homodimer, the asymmetric form is a disulfide-bonded oligomer composed of a collagenic subunit (Q) and a variable number of T catalytic subunits.Interacts with PRIMA1. The interaction with PRIMA1 is required to anchor it to the basal lamina of cells and organize into tetramers (By similarity). Isoform H generates GPI-anchored dimers, disulfide linked. Isoform T generates multiple structures, ranging from monomers and dimers to collagen-tailed and hydrophobic-tailed forms, in which catalytic tetramers are associated with anchoring proteins that attach them to the basal lamina or to cell membranes. In the collagen-tailed forms, isoform T subunits are associated with a specific collagen, COLQ, which triggers the formation of isoform T tetramers, from monomers and dimers. Isoform R may be monomeric.
Subcellular locationIsoform H: Cell membrane, Lipid-anchor, GPI- anchor. Cell junction, synapse.,Isoform T: Cell membrane, Peripheral membrane protein. Cell junction, synapse. Note=Attached to the membrane through disulfide linkage with the collagenic subunit, itself bound to the membrane.Cell junction, synapse. Secreted (By similarity). Cell membrane, Peripheral membrane protein (By similarity).,Isoform T: Nucleus. Note=Only observed in apoptotic nuclei.,Isoform H: Cell membrane, Lipid-anchor, GPI- anchor, Extracellular side (By similarity).
Cofactor



SubstratesProductsintermediates
KEGG-idC01996C00001C00114C00033I00124I00125I00126
CompoundAcetylcholineH2OCholineAcetatePeptidyl-Ser-tetrahedral intermediate (with previous acetylcholine carboxylic-ester)Acetyl-enzyme (Peptidyl-Ser-acetyl group)Peptidyl-Ser-acetyl-tetrahedral-intermediate
Typeamine group,carbohydrateH2Oamine group,carbohydratecarboxyl group


1acjAUnbound
UnboundUnboundUnboundUnboundUnbound
1aclAAnalogue:DME
UnboundUnboundUnboundUnboundUnbound
1amnAUnbound
UnboundUnboundTransition-state-analogue:NAFUnboundUnbound
1ax9AUnbound
Analogue:EDRUnboundUnboundUnboundUnbound
1cfjAUnbound
UnboundUnboundUnboundUnboundTransition-state-analogue:_GB
1dx6AUnbound
Analogue:GNTUnboundUnboundUnboundUnbound
1e3qAUnbound
UnboundUnboundUnboundUnboundUnbound
1e66AUnbound
UnboundUnboundUnboundUnboundUnbound
1ea5AUnbound
UnboundUnboundUnboundUnboundUnbound
1eeaAUnbound
UnboundUnboundUnboundUnboundUnbound
1eveAUnbound
UnboundUnboundUnboundUnboundUnbound
1fssAUnbound
UnboundUnboundUnboundUnboundUnbound
1gpkAUnbound
UnboundUnboundUnboundUnboundUnbound
1gpnAUnbound
UnboundUnboundUnboundUnboundUnbound
1gqrAUnbound
Analogue:SAFUnboundUnboundIntermediate-analogue:EMMUnbound
1gqsAUnbound
Analogue:SAFUnboundUnboundUnboundUnbound
1h22AUnbound
UnboundUnboundUnboundUnboundUnbound
1h23AUnbound
UnboundUnboundUnboundUnboundUnbound
1hbjAUnbound
UnboundUnboundUnboundUnboundTransition-state-analogue:FBQ
1jjbAUnbound
UnboundUnboundUnboundUnboundUnbound
1oceAUnbound
UnboundUnboundUnboundIntermediate-analogue:MF2Unbound
1qidAUnbound
UnboundUnboundUnboundUnboundUnbound
1qieAUnbound
UnboundUnboundUnboundUnboundUnbound
1qifAUnbound
UnboundUnboundUnboundUnboundUnbound
1qigAUnbound
UnboundUnboundUnboundUnboundUnbound
1qihAUnbound
UnboundUnboundUnboundUnboundUnbound
1qiiAUnbound
UnboundUnboundUnboundUnboundUnbound
1qijAUnbound
UnboundUnboundUnboundUnboundUnbound
1qikAUnbound
UnboundUnboundUnboundUnboundUnbound
1qimAUnbound
UnboundUnboundUnboundUnboundUnbound
1qtiAUnbound
Analogue:GNTUnboundUnboundUnboundUnbound
1somAUnbound
UnboundUnboundUnboundUnboundTransition-state-analogue:VXA
1votAUnbound
UnboundUnboundUnboundUnboundUnbound
1vxoAUnbound
UnboundUnboundUnboundUnboundTransition-state-analogue:VXA
1vxrAUnbound
UnboundUnboundTransition-state-analogue:_VXUnboundUnbound
1w4lAUnbound
Analogue:GL8UnboundUnboundUnboundUnbound
1w6rAUnbound
Analogue:GNTUnboundUnboundUnboundUnbound
1w75AUnbound
UnboundUnboundUnboundUnboundUnbound
1w75BUnbound
UnboundUnboundUnboundUnboundUnbound
1w76AUnbound
Analogue:GNTUnboundUnboundUnboundUnbound
1w76BUnbound
Analogue:GNTUnboundUnboundUnboundUnbound
2aceAUnbound
UnboundUnboundTransition-state-bound:ACHUnboundUnbound
2ackAUnbound
Analogue:EDRUnboundUnboundUnboundUnbound
2dfpAUnbound
UnboundUnboundUnboundUnboundTransition-state-analogue:MIS
1b41AUnbound
UnboundUnboundUnboundUnboundUnbound
1f8uAUnbound
UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
PDB;1acj & Swiss-prot;P22303, P04058
pdbCatalytic residuesModified residuesMain-chain involved in catalysiscomment
1acjASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1aclASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1amnASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1ax9ASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1cfjASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1dx6ASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1e3qASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1e66ASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1ea5ASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1eeaASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1eveASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1fssASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1gpkASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1gpnASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1gqrASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1gqsASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1h22ASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1h23ASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1hbjASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1jjbASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1oceASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1qidASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1qieASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1qifASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1qigASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1qihASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1qiiASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1qijASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1qikASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1qimASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1qtiASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1somASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1votASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1vxoASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1vxrASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1w4lASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1w6rASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1w75ASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1w75BSER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1w76ASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

1w76BSER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

2aceASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

2ackASER 200;GLU 327;HIS 440

GLY 118;GLY 119;ALA 201

2dfpA       ;GLU 327;HIS 440
MIS 200
GLY 118;GLY 119;ALA 201
Modified Ser200
1b41ASER 203;GLU 334;HIS 447

GLY 121;GLY 122;ALA 204

1f8uASER 203;GLU 334;HIS 447

GLY 121;GLY 122;ALA 204


References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.876-877
[8]Scheme 1
[20]p.838-839
[24]p.2324-2326
[36]Scheme 1
[52]Scheme 1, p.5683
[53]Fig.3

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
Medline ID91343928
PubMed ID1678899
JournalScience
Year1991
Volume253
Pages872-9
AuthorsSussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I
TitleAtomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein.
Related Swiss-protP04058
[2]
PubMed ID1396557
JournalEMBO J
Year1992
Volume11
Pages3561-8
AuthorsShafferman A, Velan B, Ordentlich A, Kronman C, Grosfeld H, Leitner M, Flashner Y, Cohen S, Barak D, Ariel N
TitleSubstrate inhibition of acetylcholinesterase: residues affecting signal transduction from the surface to the catalytic center.
[3]
PubMed ID1429564
JournalJ Biol Chem
Year1992
Volume267
Pages22122-30
Authorsle Du MH, Marchot P, Bougis PE, Fontecilla-Camps JC
Title1.9-A resolution structure of fasciculin 1, an anti-acetylcholinesterase toxin from green mamba snake venom.
[4]
CommentsMUTAGENESIS OF ACTIVE SITE RESIDUES AND OF ASP-206 AND ASP-435.
Medline ID92388112
PubMed ID1517212
JournalJ Biol Chem
Year1992
Volume267
Pages17640-8
AuthorsShafferman A, Kronman C, Flashner Y, Leitner M, Grosfeld H, Ordentlich A, Gozes Y, Cohen S, Ariel N, Barak D, et al
TitleMutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding.
Related Swiss-protP22303
[5]
PubMed ID1412713
JournalTrends Biochem Sci
Year1992
Volume17
Pages353-8
AuthorsSoreq H, Gnatt A, Loewenstein Y, Neville LF
TitleExcavations into the active-site gorge of cholinesterases.
[6]
PubMed ID8343975
JournalChem Biol Interact
Year1993
Volume87
Pages187-97
AuthorsSussman JL, Harel M, Silman I
TitleThree-dimensional structure of acetylcholinesterase and of its complexes with anticholinesterase drugs.
[7]
PubMed ID8224249
JournalFEBS Lett
Year1993
Volume334
Pages215-20
AuthorsOrdentlich A, Kronman C, Barak D, Stein D, Ariel N, Marcus D, Velan B, Shafferman A
TitleEngineering resistance to 'aging' of phosphylated human acetylcholinesterase. Role of hydrogen bond network in the active center.
[8]
PubMed ID8262242
JournalFEBS Lett
Year1993
Volume336
Pages263-6
AuthorsQian N, Kovach IM
TitleKey active site residues in the inhibition of acetylcholinesterases by soman.
[9]
CommentsX-ray crystallography
PubMed ID8415649
JournalProc Natl Acad Sci U S A
Year1993
Volume90
Pages9031-5
AuthorsHarel M, Schalk I, Ehret-Sabatier L, Bouet F, Goeldner M, Hirth C, Axelsen PH, Silman I, Sussman JL
TitleQuaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase.
Related PDB1acj,1acl
[10]
PubMed ID7821677
JournalBiochem Soc Trans
Year1994
Volume22
Pages745-9
AuthorsSilman I, Harel M, Axelsen P, Raves M, Sussman JL
TitleThree-dimensional structures of acetylcholinesterase and of its complexes with anticholinesterase agents.
[11]
PubMed ID8031791
JournalBiochemistry
Year1994
Volume33
Pages8566-76
AuthorsNair HK, Seravalli J, Arbuckle T, Quinn DM
TitleMolecular recognition in acetylcholinesterase catalysis: free-energy correlations for substrate turnover and inhibition by trifluoro ketone transition-state analogs.
[12]
PubMed ID8003956
JournalProtein Sci
Year1994
Volume3
Pages188-97
AuthorsAxelsen PH, Harel M, Silman I, Sussman JL
TitleStructure and dynamics of the active site gorge of acetylcholinesterase: synergistic use of molecular dynamics simulation and X-ray crystallography.
[13]
PubMed ID8122110
JournalScience
Year1994
Volume263
Pages1276-8
AuthorsGilson MK, Straatsma TP, McCammon JA, Ripoll DR, Faerman CH, Axelsen PH, Silman I, Sussman JL
TitleOpen "back door" in a molecular dynamics simulation of acetylcholinesterase.
[14]
PubMed ID7492545
JournalBiochemistry
Year1995
Volume34
Pages15444-52
AuthorsBarak D, Ordentlich A, Bromberg A, Kronman C, Marcus D, Lazar A, Ariel N, Velan B, Shafferman A
TitleAllosteric modulation of acetylcholinesterase activity by peripheral ligands involves a conformational transition of the anionic subsite.
[15]
PubMed ID8521480
JournalCell
Year1995
Volume83
Pages503-12
AuthorsBourne Y, Taylor P, Marchot P
TitleAcetylcholinesterase inhibition by fasciculin: crystal structure of the complex.
[16]
PubMed ID7836436
JournalJ Biol Chem
Year1995
Volume270
Pages2082-91
AuthorsOrdentlich A, Barak D, Kronman C, Ariel N, Segall Y, Velan B, Shafferman A
TitleContribution of aromatic moieties of tyrosine 133 and of the anionic subsite tryptophan 86 to catalytic efficiency and allosteric modulation of acetylcholinesterase.
[17]
PubMed ID7657613
JournalJ Biol Chem
Year1995
Volume270
Pages20391-9
AuthorsRadic Z, Quinn DM, Vellom DC, Camp S, Taylor P
TitleAllosteric control of acetylcholinesterase catalysis by fasciculin.
[18]
PubMed ID7613468
JournalProtein Sci
Year1995
Volume4
Pages703-15
Authorsvan den Born HK, Radic Z, Marchot P, Taylor P, Tsigelny I
TitleTheoretical analysis of the structure of the peptide fasciculin and its docking to acetylcholinesterase.
[19]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF COMPLEX WITH FASCICULIN.
Medline ID96363673
PubMed ID8747462
JournalStructure
Year1995
Volume3
Pages1355-66
AuthorsHarel M, Kleywegt GJ, Ravelli RB, Silman I, Sussman JL
TitleCrystal structure of an acetylcholinesterase-fasciculin complex: interaction of a three-fingered toxin from snake venom with its target.
Related PDB1fss
Related Swiss-protP04058
[20]
PubMed ID8836126
JournalBiochem J
Year1996
Volume318
Pages833-40
AuthorsShafferman A, Ordentlich A, Barak D, Stein D, Ariel N, Velan B
TitleAging of phosphylated human acetylcholinesterase: catalytic processes mediated by aromatic and polar residues of the active centre.
[21]
PubMed ID8718893
JournalBiochemistry
Year1996
Volume35
Pages10995-1004
AuthorsHosea NA, Radic Z, Tsigelny I, Berman HA, Quinn DM, Taylor P
TitleAspartate 74 as a primary determinant in acetylcholinesterase governing specificity to cationic organophosphonates.
[22]
PubMed ID8635606
JournalFEBS Lett
Year1996
Volume386
Pages65-71
AuthorsFaerman C, Ripoll D, Bon S, Le Feuvre Y, Morel N, Massoulie J, Sussman JL, Silman I
TitleSite-directed mutants designed to test back-door hypotheses of acetylcholinesterase function.
[23]
PubMed ID8849682
JournalFEBS Lett
Year1996
Volume395
Pages22-8
AuthorsVelan B, Barak D, Ariel N, Leitner M, Bino T, Ordentlich A, Shafferman A
TitleStructural modifications of the omega loop in human acetylcholinesterase.
[24]
CommentsX-ray crystallography
JournalJ Am Chem Soc
Year1996
Volume118
Pages2340-6
AuthorsHarel M, Quinn DM, Nair HK, Silman I, Sussman JL
TitleThe X-ray structure of a transition state analog complex reveals the molecular origins of the catalytic power and substrate specificity of acetylcholinesterase.
Related PDB1amn
[25]
PubMed ID8845756
JournalProtein Sci
Year1996
Volume5
Pages672-9
AuthorsMarchot P, Ravelli RB, Raves ML, Bourne Y, Vellom DC, Kanter J, Camp S, Sussman JL, Taylor P
TitleSoluble monomeric acetylcholinesterase from mouse: expression, purification, and crystallization in complex with fasciculin.
[26]
PubMed ID9202137
JournalFEBS Lett
Year1997
Volume409
Pages155-60
AuthorsPomponi M, Marta M, Colella A, Sacchi S, Patamia M, Gatta F, Capone F, Oliverio A, Pavone F
TitleStudies on a new series of THA analogues: effects of the aromatic residues that line the gorge of AChE.
[27]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID97143314
PubMed ID8989325
JournalNat Struct Biol
Year1997
Volume4
Pages57-63
AuthorsRaves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman JL
TitleStructure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A.
Related PDB1vot,2ace
Related Swiss-protP04058
[28]
PubMed ID9261870
JournalProteins
Year1997
Volume28
Pages543-55
AuthorsAlbaret C, Lacoutiere S, Ashman WP, Froment D, Fortier PL
TitleMolecular mechanic study of nerve agent O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonothioate (VX) bound to the active site of Torpedo californica acetylcholinesterase.
[29]
CommentsX-ray crystallography
PubMed ID10089512
JournalActa Crystallogr D Biol Crystallogr
Year1998
Volume54
Pages1359-66
AuthorsRavelli RB, Raves ML, Ren Z, Bourgeois D, Roth M, Kroon J, Silman I, Sussman JL
TitleStatic Laue diffraction studies on acetylcholinesterase.
Related PDB1ax9
[30]
PubMed ID9742217
JournalBiochem J
Year1998
Volume335
Pages95-102
AuthorsAriel N, Ordentlich A, Barak D, Bino T, Velan B, Shafferman A
TitleThe 'aromatic patch' of three proximal residues in the human acetylcholinesterase active centre allows for versatile interaction modes with inhibitors.
[31]
PubMed ID9691268
JournalBiophys Chem
Year1998
Volume72
Pages239-46
AuthorsPomponi M, Sacchi S, Colella A, Patamia M, Marta M
TitleThe role of TRP84 in catalytic power and the specificity of AChE.
[32]
PubMed ID9789806
JournalJ Physiol Paris
Year1998
Volume92
Pages191-4
AuthorsKryger G, Silman I, Sussman JL
TitleThree-dimensional structure of a complex of E2020 with acetylcholinesterase from Torpedo californica.
[33]
CommentsX-ray crystallography (ISBN: 0306460505)
JournalStructure and Function of Cholinesterases and Related Proteins
Year1998
Volume
Pages
AuthorsRaves ML, Giles K, Schrag JD, Schmid MF, Phillips GN, Wah C, Howard AJ, Silman I, Sussman JL
TitleQuaternary structure of tetrameric acetylcholinesterase.
Related PDB1eea
[34]
CommentsX-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
Medline ID99249780
PubMed ID10231521
JournalBiochemistry
Year1999
Volume38
Pages5714-9
AuthorsBartolucci C, Perola E, Cellai L, Brufani M, Lamba D
Title"Back door" opening implied by the crystal structure of a carbamoylated acetylcholinesterase.
Related PDB1oce
Related Swiss-protP04058
[35]
PubMed ID10433700
JournalBiochemistry
Year1999
Volume38
Pages9937-47
AuthorsLuo C, Saxena A, Smith M, Garcia G, Radic Z, Taylor P, Doctor BP
TitlePhosphoryl oxime inhibition of acetylcholinesterase during oxime reactivation is prevented by edrophonium.
[36]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID99282167
PubMed ID10353814
JournalBiochemistry
Year1999
Volume38
Pages7032-9
AuthorsMillard CB, Kryger G, Ordentlich A, Greenblatt HM, Harel M, Raves ML, Segall Y, Barak D, Shafferman A, Silman I, Sussman JL
TitleCrystal structures of aged phosphonylated acetylcholinesterase: nerve agent reaction products at the atomic level.
Related PDB1cfj,1som,2dfp
Related Swiss-protP04058
[37]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID20074924
PubMed ID10606746
JournalFEBS Lett
Year1999
Volume463
Pages321-6
AuthorsGreenblatt HM, Kryger G, Lewis T, Silman I, Sussman JL
TitleStructure of acetylcholinesterase complexed with (-)-galanthamine at 2.3 A resolution.
Related PDB1dx6
Related Swiss-protP04058
[38]
CommentsX-ray crystallography
JournalJ Am Chem Soc
Year1999
Volume121
Pages9883-4
AuthorsMillard CB, Koellner G, Ordentlich A, Shafferman A, Silman I, Sussman JL
TitleReaction products of acetylcholinesterase and VX reveal a mobile histidine in the catalytic triad.
Related PDB1vxo,1vxr
[39]
PubMed ID10521413
JournalJ Biol Chem
Year1999
Volume274
Pages30370-6
AuthorsBourne Y, Grassi J, Bougis PE, Marchot P
TitleConformational flexibility of the acetylcholinesterase tetramer suggested by x-ray crystallography.
Related Swiss-protP04058
[40]
PubMed ID9915834
JournalJ Biol Chem
Year1999
Volume274
Pages2963-70
AuthorsBourne Y, Taylor P, Bougis PE, Marchot P
TitleCrystal structure of mouse acetylcholinesterase. A peripheral site-occluding loop in a tetrameric assembly.
[41]
PubMed ID10602696
JournalJ Med Chem
Year1999
Volume42
Pages5110-9
AuthorsBarril X, Orozco M, Luque FJ
TitlePredicting relative binding free energies of tacrine-huperzine A hybrids as inhibitors of acetylcholinesterase.
[42]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID99197295
PubMed ID10368299
JournalStructure Fold Des
Year1999
Volume7
Pages297-307
AuthorsKryger G, Silman I, Sussman JL
TitleStructure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs.
Related PDB1eve
Related Swiss-protP04058
[43]
CommentsX-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 36-574.
Medline ID20508217
PubMed ID11053835
JournalActa Crystallogr D Biol Crystallogr
Year2000
Volume56
Pages1385-94
AuthorsKryger G, Harel M, Giles K, Toker L, Velan B, Lazar A, Kronman C, Barak D, Ariel N, Shafferman A, Silman I, Sussman JL
TitleStructures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II.
Related PDB1b41,1f8u
Related Swiss-protP22303
[44]
PubMed ID10801325
JournalBiochemistry
Year2000
Volume39
Pages5750-7
AuthorsWong L, Radic Z, Bruggemann RJ, Hosea N, Berman HA, Taylor P
TitleMechanism of oxime reactivation of acetylcholinesterase analyzed by chirality and mutagenesis.
[45]
PubMed ID10732982
JournalBioorg Med Chem
Year2000
Volume8
Pages653-6
AuthorsHirashima A, Kuwano E, Eto M
TitleDocking study of enantiomeric fonofos oxon bound to the active site of Torpedo californica acetylcholinesterase.
[46]
PubMed ID10669619
JournalJ Mol Biol
Year2000
Volume296
Pages713-35
AuthorsKoellner G, Kryger G, Millard CB, Silman I, Sussman JL, Steiner T
TitleActive-site gorge and buried water molecules in crystal structures of acetylcholinesterase from Torpedo californica.
[47]
PubMed ID10788331
JournalJ Mol Biol
Year2000
Volume298
Pages705-26
AuthorsVan Belle D, De Maria L, Iurcu G, Wodak SJ
TitlePathways of ligand clearance in acetylcholinesterase by multiple copy sampling.
[48]
CommentsX-ray crystallography
PubMed ID10639129
JournalProc Natl Acad Sci U S A
Year2000
Volume97
Pages623-8
AuthorsWeik M, Ravelli RB, Kryger G, McSweeney S, Raves ML, Harel M, Gros P, Silman I, Kroon J, Sussman JL
TitleSpecific chemical and structural damage to proteins produced by synchrotron radiation.
Related PDB1qid,1qie,1qif,1qig,1qih,1qii,1qij,1qik,1qim
[49]
PubMed ID11171062
JournalBiochem J
Year2001
Volume353
Pages645-53
AuthorsEnyedy IJ, Kovach IM, Bencsura A
TitleMolecular dynamics study of active-site interactions with tetracoordinate transients in acetylcholinesterase and its mutants.
[50]
PubMed ID11523986
JournalBiochemistry
Year2001
Volume40
Pages10447-57
AuthorsDe Ferrari GV, Canales MA, Shin I, Weiner LM, Silman I, Inestrosa NC
TitleA structural motif of acetylcholinesterase that promotes amyloid beta-peptide fibril formation.
[51]
PubMed ID11412096
JournalBiochemistry
Year2001
Volume40
Pages7433-45
AuthorsKaplan D, Ordentlich A, Barak D, Ariel N, Kronman C, Velan B, Shafferman A
TitleDoes "butyrylization" of acetylcholinesterase through substitution of the six divergent aromatic amino acids in the active center gorge generate an enzyme mimic of butyrylcholinesterase?
[52]
PubMed ID11341833
JournalBiochemistry
Year2001
Volume40
Pages5682-90
AuthorsMassiah MA, Viragh C, Reddy PM, Kovach IM, Johnson J, Rosenberry TL, Mildvan AS
TitleShort, strong hydrogen bonds at the active site of human acetylcholinesterase: proton NMR studies.
[53]
CommentsX-ray crystallography
PubMed ID11563919
JournalJ Med Chem
Year2001
Volume44
Pages3203-15
AuthorsDoucet-Personeni C, Bentley PD, Fletcher RJ, Kinkaid A, Kryger G, Pirard B, Taylor A, Taylor R, Taylor J, Viner R, Silman I, Sussman JL, Greenblatt HM, Lewis T
TitleA structure-based design approach to the development of novel, reversible AChE inhibitors.
Related PDB1hbj
[54]
PubMed ID11708910
JournalJ Med Chem
Year2001
Volume44
Pages4062-71
AuthorsYu Q, Holloway HW, Flippen-Anderson JL, Hoffman B, Brossi A, Greig NH
TitleMethyl analogues of the experimental Alzheimer drug phenserine: synthesis and structure/activity relationships for acetyl- and butyrylcholinesterase inhibitory action.
[55]
PubMed ID11449566
JournalJ Mol Graph Model
Year2001
Volume19
Pages288-96, 374-8
AuthorsPilger C, Bartolucci C, Lamba D, Tropsha A, Fels G
TitleAccurate prediction of the bound conformation of galanthamine in the active site of Torpedo californica acetylcholinesterase using molecular docking.
[56]
PubMed ID11567086
JournalProtein Sci
Year2001
Volume10
Pages1953-61
AuthorsWeik M, Ravelli RB, Silman I, Sussman JL, Gros P, Kroon J
TitleSpecific protein dynamics near the solvent glass transition assayed by radiation-induced structural changes.
[57]
CommentsX-ray crystallography
PubMed ID11119642
JournalProteins
Year2001
Volume42
Pages182-91
AuthorsBartolucci C, Perola E, Pilger C, Fels G, Lamba D
TitleThree-dimensional structure of a complex of galanthamine (Nivalin) with acetylcholinesterase from Torpedo californica: implications for the design of new anti-Alzheimer drugs.
Related PDB1qti
[58]
PubMed ID12069617
JournalAcc Chem Res
Year2002
Volume35
Pages332-40
AuthorsShen T, Tai K, Henchman RH, McCammon JA
TitleMolecular dynamics of acetylcholinesterase.
[59]
CommentsX-ray crystallography
PubMed ID12351819
JournalActa Crystallogr D Biol Crystallogr
Year2002
Volume58
Pages1765-71
AuthorsFelder CE, Harel M, Silman I, Sussman JL
TitleStructure of a complex of the potent and specific inhibitor BW284C51 with Torpedo californica acetylcholinesterase.
Related PDB1e3q
[60]
PubMed ID12081473
JournalBiochemistry
Year2002
Volume41
Pages8245-52
AuthorsBarak D, Kaplan D, Ordentlich A, Ariel N, Velan B, Shafferman A
TitleThe aromatic "trapping" of the catalytic histidine is essential for efficient catalysis in acetylcholinesterase.
[61]
CommentsX-ray crystallography
PubMed ID11888271
JournalBiochemistry
Year2002
Volume41
Pages3555-64
AuthorsBar-On P, Millard CB, Harel M, Dvir H, Enz A, Sussman JL, Silman I
TitleKinetic and structural studies on the interaction of cholinesterases with the anti-Alzheimer drug rivastigmine.
Related PDB1gqr,1gqs
[62]
CommentsX-ray crystallography
PubMed ID12196020
JournalBiochemistry
Year2002
Volume41
Pages10810-8
AuthorsDvir H, Jiang HL, Wong DM, Harel M, Chetrit M, He XC, Jin GY, Yu GL, Tang XC, Silman I, Bai DL, Sussman JL
TitleX-ray structures of Torpedo californica acetylcholinesterase complexed with (+)-huperzine A and (-)-huperzine B: structural evidence for an active site rearrangement.
Related PDB1gpk,1gpn
[63]
CommentsX-ray crystallography
PubMed ID11863435
JournalBiochemistry
Year2002
Volume41
Pages2970-81
AuthorsDvir H, Wong DM, Harel M, Barril X, Orozco M, Luque FJ, Munoz-Torrero D, Camps P, Rosenberry TL, Silman I, Sussman JL
Title3D structure of Torpedo californica acetylcholinesterase complexed with huprine X at 2.1 A resolution: kinetic and molecular dynamic correlates.
Related PDB1e66
[64]
PubMed ID11904227
JournalBiochim Biophys Acta
Year2002
Volume1594
Pages313-24
AuthorsMasson P, Schopfer LM, Bartels CF, Froment MT, Ribes F, Nachon F, Lockridge O
TitleSubstrate activation in acetylcholinesterase induced by low pH or mutation in the pi-cation subsite.
[65]
PubMed ID11920879
JournalElectrophoresis
Year2002
Volume23
Pages930-7
AuthorsRochu D, Renault F, Masson P
TitleDetection of unwanted protein-bound ligands by capillary zone electrophoresis: the case of hidden ligands that stabilize cholinesterase conformation.
[66]
CommentsX-ray crystallography
PubMed ID12095250
JournalJ Mol Biol
Year2002
Volume320
Pages721-5
AuthorsKoellner G, Steiner T, Millard CB, Silman I, Sussman JL
TitleA neutral molecule in a cation-binding site: specific binding of a PEG-SH to acetylcholinesterase from Torpedo californica.
Related PDB1jjb
[67]
PubMed ID12731886
JournalBiochemistry
Year2003
Volume42
Pages5438-52
AuthorsJohnson JL, Cusack B, Davies MP, Fauq A, Rosenberry TL
TitleUnmasking tandem site interaction in human acetylcholinesterase. Substrate activation with a cationic acetanilide substrate.
[68]
PubMed ID12601798
JournalBiopolymers
Year2003
Volume68
Pages395-406
AuthorsZeev-Ben-Mordehai T, Silman I, Sussman JL
TitleAcetylcholinesterase in motion: visualizing conformational changes in crystal structures by a morphing procedure.
[69]
PubMed ID12505979
JournalEMBO J
Year2003
Volume22
Pages1-12
AuthorsBourne Y, Taylor P, Radic Z, Marchot P
TitleStructural insights into ligand interactions at the acetylcholinesterase peripheral anionic site.
[70]
PubMed ID14622273
JournalEur J Biochem
Year2003
Volume270
Pages4447-58
AuthorsSaxena A, Fedorko JM, Vinayaka CR, Medhekar R, Radic Z, Taylor P, Lockridge O, Doctor BP
TitleAromatic amino-acid residues at the active and peripheral anionic sites control the binding of E2020 (Aricept) to cholinesterases.
[71]
CommentsX-ray crystallography
JournalJ Am Chem Soc
Year2003
Volume125
Pages363-3
AuthorsWong DM, Greenblatt HM, Dvir H, Carlier PR, Han YF, Pang YP, Silman I, Sussman JL
TitleAcetylcholinesterase complexed with bivalent ligands related to huperzine A: experimental evidence for species-dependent protein-ligand complementarity.
Related PDB1h22,1h23
[72]
PubMed ID12759360
JournalJ Biol Chem
Year2003
Volume278
Pages30905-11
AuthorsShi J, Tai K, McCammon JA, Taylor P, Johnson DA
TitleNanosecond dynamics of the mouse acetylcholinesterase cys69-cys96 omega loop.
[73]
PubMed ID14584959
JournalJ Med Chem
Year2003
Volume46
Pages5087-90
AuthorsZaheer-Ul-Haq ZU, Wellenzohn B, Liedl KR, Rode BM
TitleMolecular docking studies of natural cholinesterase-inhibiting steroidal alkaloids from Sarcococca saligna.
[74]
PubMed ID15023064
JournalBiochemistry
Year2004
Volume43
Pages3129-36
AuthorsKaplan D, Barak D, Ordentlich A, Kronman C, Velan B, Shafferman A
TitleIs aromaticity essential for trapping the catalytic histidine 447 in human acetylcholinesterase?
[75]
PubMed ID15078872
JournalJ Biol Chem
Year2004
Volume279
Pages26612-8
AuthorsBoyd AE, Dunlop CS, Wong L, Radic Z, Taylor P, Johnson DA
TitleNanosecond dynamics of acetylcholinesterase near the active center gorge.
[76]
PubMed ID15267237
JournalJ Med Chem
Year2004
Volume47
Pages3991-9
AuthorsCavalli A, Bottegoni G, Raco C, De Vivo M, Recanatini M
TitleA computational study of the binding of propidium to the peripheral anionic site of human acetylcholinesterase.
[77]
PubMed ID15563167
JournalJ Am Chem Soc
Year2004
Volume126
Pages15405-11
AuthorsGreenblatt HM, Guillou C, Guenard D, Argaman A, Botti S, Badet B, Thal C, Silman I, Sussman JL
TitleThe complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design.
Related PDB1w4l,1w6r,1w75,1w76

comments
According to the literature [1] & [24], this enzyme has got a similar catalytic triad to that of serine proteases, including trypsin (D00197 in EzCatDB), although glutamate is used instead of aspartate as a modulator.
Moreover, normally two amide groups form an oxyanion hole, but this enzyme use three amide groups (from Gly118, Gly119 & Ala201) to form it for the transition-state stabilization. (Ser200 acts as a nucleophile, whereas His440 acts as a general acid-base.)

createdupdated
2004-03-192012-02-21


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 2010)
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)

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