Three-dimensional structure of the biotin carboxylase subunit of acetyl-CoA carboxylase
GL Waldrop, I Rayment, HM Holden - Biochemistry, 1994 - ACS Publications
GL Waldrop, I Rayment, HM Holden
Biochemistry, 1994•ACS PublicationsRevised Manuscript Received June 8, 1994® abstract: Acetyl-CoA carboxylase is found in
all animals, plants, and bacteria and catalyzes the first committed step in fatty acid synthesis.
It is a multicomponent enzyme containing a biotin carboxylase activity, a biotin carboxyl
carrier protein, and a carboxyltransferase functionality. Here we report the X-ray structure of
the biotin carboxylase component from Escherichia coli determined to 2.4-A resolution. The
structure was solved by a combination of multiple isomorphous replacement and electron …
all animals, plants, and bacteria and catalyzes the first committed step in fatty acid synthesis.
It is a multicomponent enzyme containing a biotin carboxylase activity, a biotin carboxyl
carrier protein, and a carboxyltransferase functionality. Here we report the X-ray structure of
the biotin carboxylase component from Escherichia coli determined to 2.4-A resolution. The
structure was solved by a combination of multiple isomorphous replacement and electron …
Revised Manuscript Received June 8, 1994® abstract: Acetyl-CoA carboxylase is found in all animals, plants, and bacteria and catalyzes the first committed step in fatty acid synthesis. It is a multicomponent enzyme containing a biotin carboxylase activity, a biotin carboxyl carrier protein, and a carboxyltransferase functionality. Here we report the X-ray structure of the biotin carboxylase component from Escherichia coli determined to 2.4-A resolution. The structure was solved by a combination of multiple isomorphous replacement and electron density modification procedures. The overallfold of the molecule may be described in terms of three structural domains. The N-terminal region, formed by Met 1—lie 103, adopts a dinucleotide binding motif withfive strands of parallel/3-sheet flanked on either side by a-helices. The “B-domain” extends from the main body of the subunit where it folds into two a-helical regions and three strands of/3-sheet. Following the excursion into the B-domain, the polypeptide chain folds back into the body of the protein where it forms an eight-stranded antiparallel/3-sheet. In addition to this major secondary structural element, the C-terminal domain also contains a smaller three-stranded antiparallel/3-sheet and seven a-helices. The active site of the enzyme has been identified tentatively by a difference Fourier map calculated between X-ray data from the native crystals and from crystals soaked in a Ag+/biotin complex. Those amino acid residues believed to form part of the active site pocket include His 209-Glu 211, His 236-Glu 241, Glu 276, lie 287-Glu 296, and Arg 338. The structure presented here represents the first X-ray model of a biotin-dependent carboxylase.
Acetyl-CoA carboxylase catalyzes the first committed and one of the regulated steps in the biosynthesis of long-chain fatty acids (Wakil et al., 1983). The enzyme, found in all animals, plants, and bacteria, catalyzes the biotin-dependent carboxylation of acetyl-CoA to form malonyl-CoA in a two-step reaction mechanism (Lane etal., 1974; Alberts & Vagelos, 1972):
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