PDBsum entry: 1uyv

Transferase

PDB id: 1uyv

Contents

Protein chains

572 a.a. *

Waters ×192

* Residue conservation analysis

PDB id:

1uyv

Name:

Transferase

Title:

Acetyl-coa carboxylase carboxyltransferase domain l1705i/ v1967i mutant

Structure:

Acetyl-coa carboxylase. Chain: a, b, c. Fragment: carboxyltransferase, residues 1482-2218. Synonym: acc. Engineered: yes. Mutation: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PDB file)

Resolution:

2.60Å R-factor: 0.212 R-free: 0.237

Authors:

H.Zhang,B.Tweel,L.Tong

Key ref:

H.Zhang et al. (2004). Molecular basis for the inhibition of the carboxyltransferase domain of acetyl-coenzyme-A carboxylase by haloxyfop and diclofop. Proc Natl Acad Sci U S A, 101, 5910-5915. PubMed id: 15079078 DOI: 10.1073/pnas.0400891101

Date:

02-Mar-04 Release date: 29-Mar-04

Protein chains

Q00955  (ACAC_YEAST) -  Acetyl-CoA carboxylase

Seq: 2233 a.a.

Struc: 572 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: E.C.6.3.4.14 - Biotin carboxylase.
• Reaction: ATP + biotin-[carboxyl-carrier-protein] + CO₂ = ADP + phosphate + carboxy-biotin-[carboxyl-carrier-protein]
• Enzyme class 3: E.C.6.4.1.2 - Acetyl-CoA carboxylase.
• Reaction: ATP + acetyl-CoA + HCO₃^- = ADP + phosphate + malonyl-CoA
• Cofactor: Biotin

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

 Gene Ontology (GO) functional annotation 

• Biochemical function: ligase activity (1 term)

reference

DOI no: 10.1073/pnas.0400891101

Proc Natl Acad Sci U S A 101:5910-5915 (2004)

PubMed id: 15079078

Molecular basis for the inhibition of the carboxyltransferase domain of acetyl-coenzyme-A carboxylase by haloxyfop and diclofop.

H.Zhang, B.Tweel, L.Tong.

ABSTRACT

Acetyl-CoA carboxylases (ACCs) are crucial for the metabolism of fatty acids, making these enzymes important targets for the development of therapeutics against obesity, diabetes, and other diseases. The carboxyltransferase (CT) domain of ACC is the site of action of commercial herbicides, such as haloxyfop, diclofop, and sethoxydim. We have determined the crystal structures at up to 2.5-A resolution of the CT domain of yeast ACC in complex with the herbicide haloxyfop or diclofop. The inhibitors are bound in the active site, at the interface of the dimer of the CT domain. Unexpectedly, inhibitor binding requires large conformational changes for several residues in this interface, which create a highly conserved hydrophobic pocket that extends deeply into the core of the dimer. Two residues that affect herbicide sensitivity are located in this binding site, and mutation of these residues disrupts the structure of the domain. Other residues in the binding site are strictly conserved among the CT domains.

Selected figure(s)

Figure 1.
Fig. 1. Crystal structure of CT domain in complex with haloxyfop. (A) Domain organization of yeast ACC. The N and C subdomains of CT are colored in cyan and yellow, respectively. (B) Chemical structures of the herbicides (R)-haloxyfop and (R)-diclofop. (C) Final 2F[o] - F[c] electron density at 2.8-Å resolution for haloxyfop, contoured at 1 . (D) Schematic stereodrawing of the structure of yeast CT domain dimer in complex with haloxyfop. The N domains of the two monomers are colored in cyan and magenta, and the C domains are colored in yellow and green. The inhibitor is shown in stick models, in black for carbon atoms. The CoA molecule is shown for reference (11), in gray. C was produced with SETOR (28), and D was produced with RIBBONS (29).

Figure 2.
Fig. 2. The binding mode of haloxyfop. (A) Stereographic drawing showing the binding site for haloxyfop. The N domain of one monomer is colored in cyan, and the C domain of the other monomer is in green. The side chains of residues in the binding site are shown in yellow and magenta, respectively. The dashed segment indicates the disordered residues 1959'-1964'. The drawing was produced with RIBBONS (29). (B) Schematic drawing of the interactions between haloxyfop and the CT domain. (C) Overlay of the binding mode of haloxyfop (in black) and diclofop (in green). The conformations of residues Tyr-1738 and Phe-1956' in the haloxyfop (yellow and magenta) and diclofop (cyan) complexes are also shown.

Figures were selected by an automated process.