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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1q6x

E.C. namecholine O-acetyltransferase
SpeciesRattus norvegicus (Rat)
E.C. Number (IntEnz) 2.3.1.6
CSA Homologues of 1q6xThere are 24 Homologs
CSA Entries With UniProtID P32738
CSA Entries With EC Number 2.3.1.6
PDBe Entry 1q6x
PDBSum Entry 1q6x
MACiE Entry 1q6x

Literature Report

IntroductionCholine 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.
MechansimHis 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.
Reaction

Catalytic Sites for 1q6x

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA334334macie:sideChainActs as a general base, extracting a proton from the attacking hydroxyl group of choline. Later protonates the departing sulphydryl group of CoA.
SerA550550macie:sideChainHydrogen bonding from side chain OH stabilises the tetrahedral intermediate/transition state.
TyrA9595macie:sideChainSteric 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.
ProA108108macie:sideChainSteric 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.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisB334334macie:sideChainActs as a general base, extracting a proton from the attacking hydroxyl group of choline. Later protonates the departing sulphydryl group of CoA.
SerB550550macie:sideChainHydrogen bonding from side chain OH stabilises the tetrahedral intermediate/transition state.
TyrB9595macie:sideChainSteric 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.
ProB108108macie:sideChainSteric 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.

Literature References

Notes:
Cai Y
Choline acetyltransferase structure reveals distribution of mutations that cause motor disorders.
EMBO J 2004 23 2047-2058
PubMed: 15131697
Jogl G
Crystal structure of carnitine acetyltransferase and implications for the catalytic mechanism and fatty acid transport.
Cell 2003 112 113-122
PubMed: 12526798
Wu D
Structure of human carnitine acetyltransferase. Molecular basis for fatty acyl transfer.
J Biol Chem 2003 278 13159-13165
PubMed: 12562770
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