Introduction:
Acetylcholinesterase catalyses the hydrolysis of acetylchline(neurotransmitter)
thereby shortening nerve impulse duration to only a millisecond or so.
Inactivation of acetylcholineterase causes disruption of regular sequence
of nerve impulses which can be deleterious to organism. The protein
structure of Acetylcholinesterase in a complex with tacrine was characterized
via X-ray crystallography and the resulting structure(1ACJ) was deposited
in the PDB. This choice of protein-ligand complex was probably
due to the researchers interest in tacrine, an Acetylcholinesterase Inhibitor,
which showed promise as a drug used to slow progression of Alzheimer's
disease; it works by inhibiting acetylcholinestere thus increasing levels
of acetylcholine, which is found at low levels in Alzheimer's patients.
CATH Results
Class: Alpha Beta
Architecture: 3-Layer(aba) Sandwich
T: Rossman fold
H: Thioesterase
SCOP:
1. Root: scop
2. Class: Alpha and beta proteins (a/b)
3. Fold: alpha/beta-Hydrolases
4. Superfamily: alpha/beta-Hydrolases
5. Family: Acetylcholinesterase-like
.Root: scop
2.Class: Alpha and beta proteins (a/b)
Mainly parallel beta sheets (beta-alpha-beta
units)
3.Fold: alpha/beta-Hydrolases
core: 3 layers, a/b/a; mixed beta-sheet of
8 strands, order 12435678, strand 2 is antiparallel to the rest
4.Superfamily: alpha/beta-Hydrolases
many members have left-handed crossover connection
between strand 8 and
5.Family: Acetylcholinesterase-like
6.Protein: Acetylcholinesterase
7.Species: Electric ray (Torpedo californica)
Sequence and secondary structure
Each residue in the sequence is reported as a single letter code. Secondary
structure is calculated and described
according to an implementation of the method of Kabsch and Sander (1983)
Biopolymers 22, 2577-2637. The
assignments are: H=helix; B=residue in isolated beta bridge; E=extended
beta strand; G=310 helix; I=pi helix;
T=hydrogen bonded turn; S=bend
1 DDHSELLVNT KSGKVMGTRV PVLSSHISAF LGIPFAEPPV GNMRFRRPEP
SEEEE TTEEEE EEE EETTEEEEEE E EE EE GGGTTS EE
51 KKPWSGVWNA STYPNNCQQY VDEQFPGFSG SEMWNPNREM SEDCLYLNIW
SSEEE BS B
TTTTTHH HHTTS S B S EEEEE
101 VPSPRPKSTT VMVWIYGGGF YSGSSTLDVY NGKYLAYTEE VVLVSLSYRV
E SS SSB EEEEE STT T S SGGG TTHHHHHHHT
EEEE
151 GAFGFLALHG SQEAPGNVGL LDQRMALQWV HDNIQFFGGD PKTVTIFGES
HHHHH TT SSS S HHH HHHHHHHHHH HHHGGGGTB TTSEEEEEET
201 AGGASVGMHI LSPGSRDLFR RAILQSGSPN CPWASVSVAE GRRRAVELGR
HHHHHHHHHH HTHHHHTT S EEEEES TT TTTS EEHHH HHHHHHHHHH
251 NLNCNLNSDE ELIHCLREKK PQELIDVEWN VLPFDSIFRF SFVPVIDGEF
HTT S HH HHHHHHHHTT HHHHHHHHGG G SS SS SS
EE SSS
301 FPTSLESMLN SGNFKKTQIL LGVNKDEGSF FLLYGAPGFS KDSESKISRE
SSS HHHHHH HT S S EE EEEESB SHH HHHHHTTTTT TTS
HH
351 DFMSGVKLSV PHANDLGLDA VTLQYTDWMD DNNGIKNRDG LDDIVGDHNV
HHHHHHHHH TT HHHHHH HHHHH GGG TT HHHHHHH HHHHHHHHHT
401 ICPLMHFVNK YTKFGNGTYL YFFNHRASNL VWPEWMGVIH GYEIEFVFGL
HHHHHHHHHH HHTTSS EEE EEE TT S GGG SBT TTTHHHHTTG
451 PLVKELNYTA EEEALSRRIM HYWATFAKTG NPNEPHSQES KWPLFTTKEQ
GGTGGG H HHHHHHHHHH HHHHHHHHTS SSS
SSS
501 KFIDLNTEPM KVHQRLRVQM CVFWNQFLPK LLNATET
EEEEESSSS EEESTTHHH HHHHHTHHHH HHHH
CLUSTAL W (1.82) multiple sequence alignment
1QON_A
-RLVVQTSSGPVRGRSVTVQGREVHVYTGIPYAKPPVEDLRFRKPVPAEPWHGVLDATGL 59
1ACJ__ SELLVNTKSGKVMGTRVPVLSSHISAFLGIPFAEPPVGNMRFRRPEPKKPWSGVWNASTY
60
1AKN__ -LGSVYTEGGFVEGVNKKLS---IDIFKGIPFAAAPKA---LEKPERHPGWQGTLKAKSF
53
1QE3_A THQIVTTQYGKVKG----TTENGVHKWKGIPYAKPPVGQWRFKAPEPPEVWEDVLDATAY
56
* *. * * * : : ***:*
.* :. * * .. .*.
1QON_A SATCVQERYEYFPGFSGEEIWNPNTNVSEDCLYINVWAPAKARLGLPILIWIYGGGFMTG
119
1ACJ__ PNNCQQYVDEQFPGFSGSEMWNPNREMSEDCLYLNIWVPSPRPKSTTVMVWIYGGGFYSG
120
1AKN__ KKRCLQATLTYG---------------NEDCLYLNIWVPQGVSHDLPVMIWIYGGAFLMG
98
1QE3_A GPICPQPSDLLSLSYTELP------RQSEDCLYVNVFAPDTPSQNLPVMVWIHGGAFYLG
110
* *
.*****:*::.* . .:::**:**.* *
1QON_A SATLDIYNADIMAAVGNVIVASFQYRVGAFGFLHLAPAEEAPGNVGLWDQALAIRWLKDN
179
1ACJ__ SSTLDVYNGKYLAYTEEVVLVSLSYRVGAFGFLALHGSQEAPGNVGLLDQRMALQWVHDN
180
1AKN__ ASQGYLYDGEEIATRGNVIVVTFNYRVGPLGFLSTGDSN-LPGNYGLWDQHMAIAWVKRN
157
1QE3_A AGSEPLYDGSKLAAQGEVIVVTLNYRLGPFGFLHLSSDEAYSDNLGLLDQAAALKWVREN
170
:. :*:.. :* :*::.::.**:*.:***
: ..* ** ** *: *:: *
1QON_A AHAFGGNPEWMTLFGESAGSSSVNAQLMSPVTRGLVKRGMMQSGTMNAPWSHMTSEKAVE
239
1ACJ__ IQFFGGDPKTVTIFGESAGGASVGMHILSPGSRDLFRRAILQSGSPNCPWASVSVAEGRR
240
1AKN__ IEAFGGDPDNITLFGESAGGASVSLQTLSPYNKGLIKRAISQSGVGLCPWAIQ--QDPLF
215
1QE3_A ISAFGGDPDNVTVFGESAGGMSIAALLAMPAAKGLFQKAIMESGAS----RTMTKEQAAS
226
***:*. :*:******. *: * :.*.::.: :**
.
1QON_A IGKALINDCNCNASMLAHVMSCMRSVDAKTISVQQWN--SYSGILSFPSAPTIDGAFLPA
297
1ACJ__ RAVELGRNLNCNLNSDEELIHCLREKKPQELIDVEWNVLPFDSIFRFSFVPVIDGEFFPT
300
1AKN__ WAKRIAEKVGCPVDDTSKMAGCLKITDPRALTLAYKLP---PKLHYLSFVPVIDGDFIPD
272
1QE3_A TAAAFLQVLGINESQLDRLHTVAAEDLLKAADQLREKE----NIFQLFFQPALDPKTLPE
282
. : . . . .:
:
: : *.:* :*
1QON_A DPMTLMKTADLKDYDILMGNVRDEGTYFLLYDFDYFDKDDATALPRDKYLEIMNNIFGKA
357
1ACJ__ SLESMLNSGNFKKTQILLGVNKDEGSFFLLYGAPGFSKDSESKISREDFMSGVKLSVPHA
360
1AKN__ DPVNLY--ANAADVDYIAGTNDMDGHLFVGMDVPAIN----SDVTEEDFYKLVSGLTVTK
326
1QE3_A EPEKSIAEGAASGIPLLIGTTRDEGYLFFTPDSDVHS-----------------------
319
. . . : *
:* *. . .
1QON_A TQAEREAIIFQYTSWEG-NPGYQNQQQIGRAVGDHFFTCPTNEYAQALAERGASVHYYYF
416
1ACJ__ NDLGLDAVTLQYTDWMDDNNGIKNRDGLDDIVGDHNVICPLMHFVNKYTKFGNGTYLYFF
420
1AKN__ GLRGANATYEVYTEPWAQDSQETRKKTMVDLETDILFLIPTKIAVAQHKSHAANTYTYLF
386
1QE3_A -QETLDAAAEKAADLYP-----RSLESQIHMMTDLLFWRPAVAYASAQSHYAP-VWMYRF
372
:* :.
. * . *
. . . * *
1QON_A THRTSTSLWGEWMGVLHGDEIEYFFGQPLNNSLQYRPVERELGKRMLSAVIEFAKTGNPA
476
1ACJ__ NHRASNLVWPEWMGVIHGYEIEFVFGLPLVKELNYTAEEEALSRRIMHYWATFAKTGNPN
480
1AKN__ SQPSRMPIYP--MGADHADDLQYVFGKPFATPLGYRAQDRTVSKAMIAYWTNFARTGDPN
444
1QE3_A DWHPEKPPYN---KAFHALELPFVFGNLRMAKAEITDEVKQLSHTIQSAWITFAKTGNPS
429
. : . *. :: :.**
. :.: : **:**:*
1QON_A Q---DGEEWPNFSKEDPVYYIFSTDDEKLARGPLAARCSFWNDYLPKVRSW
524
1ACJ__ EPHSQESKWPLFTTKEQKFIDLNTEPMKVHQRLRVQMCVFWNQFLPKLLNA
531
1AKN__ TGHSTVANWDPYTLEDDNYLEINKQMDSMKLHLRTNYLQFWTQTYQALPTV
495
1QE3_A T---EAVNWPAYHEETRETVILDSEITIENDPESEKRQKLF----------
467
:* : : :..:
::