PDBsum entry 1ndf

Transferase

PDB id: 1ndf

Contents

Protein chains

596 a.a. *

Ligands

152 ×2

Waters ×1070

* Residue conservation analysis

PDB id:

1ndf

Name:

Transferase

Title:

Carnitine acetyltransferase in complex with carnitine

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.

Resolution:

1.90Å R-factor: 0.200 R-free: 0.241

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

Date:

09-Dec-02 Release date: 28-Jan-03

Protein chains

P47934  (CACP_MOUSE) -  Carnitine O-acetyltransferase from Mus musculus

Seq: 626 a.a.

Struc: 596 a.a.

Enzyme reactions

• Enzyme class 2: E.C.2.3.1.137 - carnitine O-octanoyltransferase.
• Reaction: octanoyl-CoA + (R)-carnitine = O-octanoyl-(R)-carnitine + CoA
• Enzyme class 3: E.C.2.3.1.7 - carnitine O-acetyltransferase.
• Reaction: (R)-carnitine + acetyl-CoA = O-acetyl-(R)-carnitine + CoA

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

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.

ABSTRACT

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.