Expression, purification, characterization of human 3-methylcrotonyl-CoA carboxylase (MCCC)

Protein Expr Purif. 2007 Jun;53(2):421-7. doi: 10.1016/j.pep.2007.01.012. Epub 2007 Feb 2.

Abstract

The current study reports the use of baculovirus system to express functionally active human recombinant 3-methylcrotonyl-CoA carboxylase (MCCC), a heteromultimeric complex that is composed of alpha and beta subunits which are encoded by distinct genes. Using immuno-affinity purification, an efficient protocol has been developed to purify the active MCCC which appears to reside in a approximately 500-800kDa complex in Superpose-6 gel-filtration chromatography. Consistent with the native enzyme, in the recombinant human MCCC, the stoichiometry of alpha and beta subunits are at a one:one ratio. The k(cat) value of the recombinant enzyme is determined to be approximately 4.0s(-1). It also possesses K(m) values (ATP: 45+/-11microM; 3-methylcrotonyl-CoA: 74+/-7microM) similar to those reported for the native enzyme. The recombinant human MCCC described here may provide a counter-screen enzyme source for testing cross reactivity for inhibitors against acetyl-CoA carboxylases which are designed to treat obesity, type 2 diabetes and other metabolic disorders.

MeSH terms

  • Animals
  • Baculoviridae / genetics
  • Base Sequence
  • Carbon-Carbon Ligases / genetics*
  • Carbon-Carbon Ligases / isolation & purification*
  • Carbon-Carbon Ligases / metabolism
  • Cell Line
  • Chromatography, Gel
  • DNA Primers / genetics
  • Gene Expression
  • Genetic Vectors
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Protein Subunits
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Spodoptera

Substances

  • DNA Primers
  • Protein Subunits
  • Recombinant Proteins
  • Carbon-Carbon Ligases
  • methylcrotonoyl-CoA carboxylase