An asymmetric model for Na+-translocating glutaconyl-CoA decarboxylases

J Biol Chem. 2009 Oct 9;284(41):28401-28409. doi: 10.1074/jbc.M109.037762. Epub 2009 Aug 4.

Abstract

Glutaconyl-CoA decarboxylase (Gcd) couples the biotin-dependent decarboxylation of glutaconyl-CoA with the generation of an electrochemical Na(+) gradient. Sequencing of the genes encoding all subunits of the Clostridium symbiosum decarboxylase membrane complex revealed that it comprises two distinct biotin carrier subunits, GcdC(1) and GcdC(2), which differ in the length of a central alanine- and proline-rich linker domain. Co-crystallization of the decarboxylase subunit GcdA with the substrate glutaconyl-CoA, the product crotonyl-CoA, and the substrate analogue glutaryl-CoA, respectively, resulted in a high resolution model for substrate binding and catalysis revealing remarkable structural changes upon substrate binding. Unlike the GcdA structure from Acidaminococcus fermentans, these data suggest that in intact Gcd complexes, GcdA is associated as a tetramer crisscrossed by a network of solvent-filled tunnels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidaminococcus / enzymology
  • Acyl Coenzyme A / chemistry
  • Acyl Coenzyme A / metabolism
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Carboxy-Lyases / chemistry*
  • Carboxy-Lyases / genetics
  • Carboxy-Lyases / metabolism*
  • Clostridium symbiosum / enzymology
  • Clostridium symbiosum / genetics
  • Crystallography, X-Ray
  • Glutamic Acid / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Multigene Family
  • Protein Structure, Quaternary*
  • Protein Structure, Tertiary*
  • Protein Subunits / chemistry*
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Sequence Alignment
  • Sodium / metabolism*

Substances

  • Acyl Coenzyme A
  • Bacterial Proteins
  • Protein Subunits
  • Glutamic Acid
  • crotonyl-coenzyme A
  • Sodium
  • Carboxy-Lyases
  • glutaconyl CoA decarboxylase

Associated data

  • GENBANK/FJ390113
  • GENBANK/FJ390114
  • PDB/3GF3
  • PDB/3GF7
  • PDB/3GLM
  • PDB/3GMA