PDBsum entry 2fy4

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protein ligands links
Transferase PDB id
Protein chain
589 a.a. *
Waters ×447
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Structures of ligand bound human choline acetyltransferase provide insight into regulation of acetylcholine synthesis
Structure: Choline o-acetyltransferase. Chain: a. Fragment: residues 120-733. Synonym: choactase, choline acetylase, chat. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: chat. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Monomer (from PQS)
2.30Å     R-factor:   0.203     R-free:   0.240
Authors: A.R.Kim,R.J.Rylett,B.H.Shilton
Key ref:
A.R.Kim et al. (2006). Substrate binding and catalytic mechanism of human choline acetyltransferase. Biochemistry, 45, 14621-14631. PubMed id: 17144655 DOI: 10.1021/bi061536l
07-Feb-06     Release date:   12-Dec-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P28329  (CLAT_HUMAN) -  Choline O-acetyltransferase
748 a.a.
589 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 15 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Choline O-acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + choline = CoA + O-acetylcholine
Bound ligand (Het Group name = COA)
matches with 94.00% similarity
+ choline
= CoA
+ O-acetylcholine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     transferase activity, transferring acyl groups     1 term  


DOI no: 10.1021/bi061536l Biochemistry 45:14621-14631 (2006)
PubMed id: 17144655  
Substrate binding and catalytic mechanism of human choline acetyltransferase.
A.R.Kim, R.J.Rylett, B.H.Shilton.
Choline acetyltransferase (ChAT) catalyzes the synthesis of the neurotransmitter acetylcholine from choline and acetyl-CoA, and its presence is a defining feature of cholinergic neurons. We report the structure of human ChAT to a resolution of 2.2 A along with structures for binary complexes of ChAT with choline, CoA, and a nonhydrolyzable acetyl-CoA analogue, S-(2-oxopropyl)-CoA. The ChAT-choline complex shows which features of choline are important for binding and explains how modifications of the choline trimethylammonium group can be tolerated by the enzyme. A detailed model of the ternary Michaelis complex fully supports the direct transfer of the acetyl group from acetyl-CoA to choline through a mechanism similar to that seen in the serine hydrolases for the formation of an acyl-enzyme intermediate. Domain movements accompany CoA binding, and a surface loop, which is disordered in the unliganded enzyme, becomes localized and binds directly to the phosphates of CoA, stabilizing the complex. Interactions between this surface loop and CoA may function to lower the KM for CoA and could be important for phosphorylation-dependent regulation of ChAT activity.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19688192 A.G.Engel, X.M.Shen, D.Selcen, and S.M.Sine (2010).
What have we learned from the congenital myasthenic syndromes.
  J Mol Neurosci, 40, 143-153.  
19525232 H.J.Lee, B.Rakić, M.Gilbert, W.W.Wakarchuk, S.G.Withers, and N.C.Strynadka (2009).
Structural and kinetic characterizations of the polysialic acid O-acetyltransferase OatWY from Neisseria meningitidis.
  J Biol Chem, 284, 24501-24511.
PDB codes: 2wlc 2wld 2wle 2wlf 2wlg
19690370 J.Praaenikar, P.V.Afonine, G.Guncar, P.D.Adams, and D.Turk (2009).
Averaged kick maps: less noise, more signal... and probably less bias.
  Acta Crystallogr D Biol Crystallogr, 65, 921-931.  
19637146 K.D.Green, M.Fridman, and S.Garneau-Tsodikova (2009).
hChAT: a tool for the chemoenzymatic generation of potential acetyl/butyrylcholinesterase inhibitors.
  Chembiochem, 10, 2191-2194.  
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