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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1q6x
Original Entry
Title:
Transferase
Compound:
Choline o-acetyltransferase
Mutant:
No
UniProt/Swiss-Prot:
P32738-CLAT_RAT
EC Class:
2.3.1.6
Other CSA Entries:
Overview of all sites for 1q6x
Homologues of 1q6x
Entries for UniProt/Swiss-Prot: P32738
Entries for EC: 2.3.1.6
Other Databases:
PDB entry: 1q6x
PDBsum entry: 1q6x
UniProt/Swiss-Prot: P32738
IntEnz entry: 2.3.1.6
Literature Report:
Introduction:
Choline acetyltransferase synthesises the neurotransmitter acetylcholine from choline in neurones and other cell types. It catalyses the reversible transfer of an acetyl group between acetyl CoA and choline, and belongs to the choline/carnitine acyltranserase family which also includes enzymes involved in fatty acid metabolism.
Mechanism:
His 334 acts as a general base to remove the proton from the choline OH group as the oxygen attacks the carbonyl of acetyl CoA. The resulting tetrahedral oxyanion intermediate is stabilised by Ser 550. Collapse of the tetrahedral intermediate releases CoA which is protonated by the His 334. Tyr 95 and Pro 108 function to stabilise the unprotonated form of His 334 N-epsilon so that it can act as a general base in the first step of the reaction.
Sites:

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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
TYRA 95 95Sidechain
Steric strainResidue
Steric packing with His 334 forces the His 334 to adopt a strained conformation with an intraresidue hydrogen bond between N-delta and its carbonyl oxygen. This is proposed to position N-epsilon and stabilise its non-protonated, nucleophilic state.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15131697 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
PROA 108 108Sidechain
Steric strainResidue
Steric packing with His 334 forces the His 334 to adopt a strained conformation with an intraresidue hydrogen bond between N-delta and its carbonyl oxygen. This is proposed to position N-epsilon and stabilise its non-protonated, nucleophilic state.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15131697 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISA 334 334Sidechain
Acid/baseSubstrate
Acts as a general base, extracting a proton from the attacking hydroxyl group of choline. Later protonates the departing sulphydryl group of CoA.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15131697 Current protein Conservation of residue
PubMed ID 15131697 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 15131697 Current protein Mutagenesis of residue
PubMed ID 15131697 Current protein Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
SERA 550 550Sidechain
ElectrostaticTransition state
Hydrogen bonding from side chain OH stabilises the tetrahedral intermediate/transition state.
Evidence from paper Evidence concerns Evidence type
PubMed ID 12526798 Current protein Structural similarity to homologue of known mechanism
References:
1
Choline acetyltransferase structure reveals distribution of mutations that cause motor disorders.
Y. Cai and C. N. Cronin and A. G. Engel and K. Ohno and L. B. Hersh and D. W. Rodgers
EMBO J 23, (10) 2047-58, (2004).
15131697
2
Crystal structure of carnitine acetyltransferase and implications for the catalytic mechanism and fatty acid transport.
G. Jogl and L. Tong
Cell 112, (1) 113-22, (2003).
12526798
3
Structure of human carnitine acetyltransferase. Molecular basis for fatty acyl transfer.
D. Wu and L. Govindasamy and W. Lian and Y. Gu and T. Kukar and M. Agbandje-McKenna and R. McKenna
J Biol Chem 278, (15) 13159-65, (2003).
12562770
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