PDBsum entry 1ndi

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Transferase PDB id
Protein chains
596 a.a. *
COA ×2
Waters ×693
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Carnitine acetyltransferase in complex with coa
Structure: Carnitine acetyltransferase. Chain: a, b. Synonym: carnitine acetylase. Cat. Carnitine o- acetyltransferase. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.30Å     R-factor:   0.270     R-free:   0.363
Authors: G.Jogl,L.Tong
Key ref:
G.Jogl and L.Tong (2003). Crystal structure of carnitine acetyltransferase and implications for the catalytic mechanism and fatty acid transport. Cell, 112, 113-122. PubMed id: 12526798 DOI: 10.1016/S0092-8674(02)01228-X
09-Dec-02     Release date:   28-Jan-03    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P47934  (CACP_MOUSE) -  Carnitine O-acetyltransferase
626 a.a.
596 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Carnitine O-acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + carnitine = CoA + O-acetylcarnitine
Bound ligand (Het Group name = COA)
matches with 94.00% similarity
+ carnitine
= CoA
+ O-acetylcarnitine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   5 terms 
  Biological process     transport   4 terms 
  Biochemical function     transferase activity     4 terms  


DOI no: 10.1016/S0092-8674(02)01228-X Cell 112:113-122 (2003)
PubMed id: 12526798  
Crystal structure of carnitine acetyltransferase and implications for the catalytic mechanism and fatty acid transport.
G.Jogl, L.Tong.
Carnitine acyltransferases have crucial roles in the transport of fatty acids for beta-oxidation. Dysregulation of these enzymes can lead to serious diseases in humans, and they are targets for therapeutic development against diabetes. We report the crystal structures of murine carnitine acetyltransferase (CRAT), alone and in complex with its substrate carnitine or CoA. The structure contains two domains. Surprisingly, these two domains share the same backbone fold, which is also similar to that of chloramphenicol acetyltransferase and dihydrolipoyl transacetylase. The active site is located at the interface between the two domains. Carnitine and CoA are bound in deep channels in the enzyme, on opposite sides of the catalytic His343 residue. The structural information provides a molecular basis for understanding the catalysis by carnitine acyltransferases and for designing their inhibitors. Specifically, our structural information suggests that the substrate carnitine may assist the catalysis by stabilizing the oxyanion in the reaction intermediate.
  Selected figure(s)  
Figure 4.
Figure 4. The CoA Binding Site of CRAT(A) Final 2F[o]–F[c] electron density map for CoA at 2.3 Å resolution. The contour level is at 1σ. Produced with Setor (Evans, 1993).(B) Stereo diagram showing the CoA binding site of CRAT. The CoA molecule is shown in brown. Produced with Ribbons (Carson, 1987).(C) Overlap of the binding modes of CoA to CRAT (in brown) and CAT (in cyan).(D) Molecular surface of CRAT in the region of the CoA binding site. (C and D) produced with Grasp (Nicholls et al., 1991).
Figure 6.
Figure 6. The Catalytic Mechanism of Carnitine AcyltransferasesThe catalytic His343 residue can extract the proton from either carnitine or CoA. The oxyanion in the tetrahedral intermediate is stabilized by interactions with carnitine and the side chain hydroxyl of Ser554.
  The above figures are reprinted by permission from Cell Press: Cell (2003, 112, 113-122) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20822442 M.Morar, and G.D.Wright (2010).
The genomic enzymology of antibiotic resistance.
  Annu Rev Genet, 44, 25-51.  
20061394 N.T.Price, V.N.Jackson, J.Müller, K.Moffat, K.L.Matthews, T.Orton, and V.A.Zammit (2010).
Alternative exon usage in the single CPT1 gene of Drosophila generates functional diversity in the kinetic properties of the enzyme: differential expression of alternatively spliced variants in Drosophila tissues.
  J Biol Chem, 285, 7857-7865.  
19430727 A.C.Rufer, R.Thoma, and M.Hennig (2009).
Structural insight into function and regulation of carnitine palmitoyltransferase.
  Cell Mol Life Sci, 66, 2489-2501.  
19036940 N.Shah, S.Khurana, K.Cheng, and J.P.Raufman (2009).
Muscarinic receptors and ligands in cancer.
  Am J Physiol Cell Physiol, 296, C221-C232.  
19740747 T.Y.Hou, S.M.Ward, J.M.Murad, N.P.Watson, M.A.Israel, and G.E.Duffield (2009).
ID2 (inhibitor of DNA binding 2) is a rhythmically expressed transcriptional repressor required for circadian clock output in mouse liver.
  J Biol Chem, 284, 31735-31745.  
19058030 Y.Kim, H.Li, T.A.Binkowski, D.Holzle, and A.Joachimiak (2009).
Crystal structure of fatty acid/phospholipid synthesis protein PlsX from Enterococcus faecalis.
  J Struct Funct Genomics, 10, 157-163.
PDB code: 1u7n
18248603 M.J.Wolfgang, S.H.Cha, D.S.Millington, G.Cline, G.I.Shulman, A.Suwa, M.Asaumi, T.Kurama, T.Shimokawa, and M.D.Lane (2008).
Brain-specific carnitine palmitoyl-transferase-1c: role in CNS fatty acid metabolism, food intake, and body weight.
  J Neurochem, 105, 1550-1559.  
17650509 A.Faye, C.Esnous, N.T.Price, M.A.Onfray, J.Girard, and C.Prip-Buus (2007).
Rat liver carnitine palmitoyltransferase 1 forms an oligomeric complex within the outer mitochondrial membrane.
  J Biol Chem, 282, 26908-26916.  
17495187 C.Bolduc, M.Yoshioka, and J.St-Amand (2007).
Transcriptomic characterization of the long-term dihydrotestosterone effects in adipose tissue.
  Obesity (Silver Spring), 15, 1107-1132.  
17383962 H.Unno, F.Ichimaida, H.Suzuki, S.Takahashi, Y.Tanaka, A.Saito, T.Nishino, M.Kusunoki, and T.Nakayama (2007).
Structural and mutational studies of anthocyanin malonyltransferases establish the features of BAHD enzyme catalysis.
  J Biol Chem, 282, 15812-15822.
PDB codes: 2e1t 2e1u 2e1v
17696591 S.Chiechio, A.Copani, R.W.Gereau, and F.Nicoletti (2007).
Acetyl-L-carnitine in neuropathic pain: experimental data.
  CNS Drugs, 21, 31.  
16908527 K.Borthwick, V.N.Jackson, N.T.Price, and V.A.Zammit (2006).
The mitochondrial intermembrane loop region of rat carnitine palmitoyltransferase 1A is a major determinant of its malonyl-CoA sensitivity.
  J Biol Chem, 281, 32946-32952.  
16651524 M.J.Wolfgang, T.Kurama, Y.Dai, A.Suwa, M.Asaumi, S.Matsumoto, S.H.Cha, T.Shimokawa, and M.D.Lane (2006).
The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis.
  Proc Natl Acad Sci U S A, 103, 7282-7287.  
18615142 S.Chiechio, A.Copani, F.Nicoletti, and R.Gereau Iv (2006).
L-acetylcarnitine: a proposed therapeutic agent for painful peripheral neuropathies.
  Curr Neuropharmacol, 4, 233-237.  
16870616 Y.S.Hsiao, G.Jogl, and L.Tong (2006).
Crystal structures of murine carnitine acetyltransferase in ternary complexes with its substrates.
  J Biol Chem, 281, 28480-28487.
PDB codes: 2h3p 2h3u 2h3w
16781677 Y.S.Hsiao, G.Jogl, V.Esser, and L.Tong (2006).
Crystal structure of rat carnitine palmitoyltransferase II (CPT-II).
  Biochem Biophys Res Commun, 346, 974-980.
PDB code: 2h4t
16131766 A.R.Kim, T.Dobransky, R.J.Rylett, and B.H.Shilton (2005).
Surface-entropy reduction used in the crystallization of human choline acetyltransferase.
  Acta Crystallogr D Biol Crystallogr, 61, 1306-1310.  
15492013 G.Jogl, Y.S.Hsiao, and L.Tong (2005).
Crystal structure of mouse carnitine octanoyltransferase and molecular determinants of substrate selectivity.
  J Biol Chem, 280, 738-744.
PDB codes: 1xl7 1xl8 1xmc 1xmd
15579906 H.Liu, G.Zheng, M.Treber, J.Dai, and G.Woldegiorgis (2005).
Cysteine-scanning mutagenesis of muscle carnitine palmitoyltransferase I reveals a single cysteine residue (Cys-305) is important for catalysis.
  J Biol Chem, 280, 4524-4531.  
16115688 K.C.Onwueme, C.J.Vos, J.Zurita, J.A.Ferreras, and L.E.Quadri (2005).
The dimycocerosate ester polyketide virulence factors of mycobacteria.
  Prog Lipid Res, 44, 259-302.  
17191957 R.D.Gandour (2005).
Rationalizing the solution properties of zwitterions by means of computational chemistry.
  Chem Biodivers, 2, 1580-1594.  
15665331 X.Ma, J.Koepke, S.Panjikar, G.Fritzsch, and J.Stöckigt (2005).
Crystal structure of vinorine synthase, the first representative of the BAHD superfamily.
  J Biol Chem, 280, 13576-13583.
PDB code: 2bgh
15155769 A.G.Cordente, E.López-Viñas, M.I.Vázquez, J.H.Swiegers, I.S.Pretorius, P.Gómez-Puertas, F.G.Hegardt, G.Asins, and D.Serra (2004).
Redesign of carnitine acetyltransferase specificity by protein engineering.
  J Biol Chem, 279, 33899-33908.  
15591000 G.Jogl, Y.S.Hsiao, and L.Tong (2004).
Structure and function of carnitine acyltransferases.
  Ann N Y Acad Sci, 1033, 17-29.  
15123643 J.Buglino, K.C.Onwueme, J.A.Ferreras, L.E.Quadri, and C.D.Lima (2004).
Crystal structure of PapA5, a phthiocerol dimycocerosyl transferase from Mycobacterium tuberculosis.
  J Biol Chem, 279, 30634-30642.
PDB code: 1q9j
14747730 W.Lian, Y.Gu, B.Pedersen, T.Kukar, L.Govindasamy, M.Agbandje-McKenna, S.Jin, R.McKenna, and D.Wu (2004).
Crystallization and preliminary X-ray crystallographic studies on recombinant rat choline acetyltransferase.
  Acta Crystallogr D Biol Crystallogr, 60, 374-375.  
15131697 Y.Cai, C.N.Cronin, A.G.Engel, K.Ohno, L.B.Hersh, and D.W.Rodgers (2004).
Choline acetyltransferase structure reveals distribution of mutations that cause motor disorders.
  EMBO J, 23, 2047-2058.
PDB code: 1q6x
15155726 Y.S.Hsiao, G.Jogl, and L.Tong (2004).
Structural and biochemical studies of the substrate selectivity of carnitine acetyltransferase.
  J Biol Chem, 279, 31584-31589.
PDB codes: 1t7n 1t7o 1t7q
15286736 Y.Shi, and P.Burn (2004).
Lipid metabolic enzymes: emerging drug targets for the treatment of obesity.
  Nat Rev Drug Discov, 3, 695-710.  
12826662 L.Napal, J.Dai, M.Treber, D.Haro, P.F.Marrero, and G.Woldegiorgis (2003).
A single amino acid change (substitution of the conserved Glu-590 with alanine) in the C-terminal domain of rat liver carnitine palmitoyltransferase I increases its malonyl-CoA sensitivity close to that observed with the muscle isoform of the enzyme.
  J Biol Chem, 278, 34084-34089.  
12677067 M.Valle, R.Gillet, S.Kaur, A.Henne, V.Ramakrishnan, and J.Frank (2003).
Visualizing tmRNA entry into a stalled ribosome.
  Science, 300, 127-130.
PDB code: 1zc8
12877997 R.R.Ramsay, and J.H.Naismith (2003).
A snapshot of carnitine acetyltransferase.
  Trends Biochem Sci, 28, 343-346.  
14517221 S.Gobin, L.Thuillier, G.Jogl, A.Faye, L.Tong, M.Chi, J.P.Bonnefont, J.Girard, and C.Prip-Buus (2003).
Functional and structural basis of carnitine palmitoyltransferase 1A deficiency.
  J Biol Chem, 278, 50428-50434.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.