This is the first enzyme of leucine biosynthesis. A larger family of homologous proteins includes homocitrate synthase, distinct lineages of 2-isopropylmalate synthase, several distinct, uncharacterized, orthologous sets in the Archaea, and other related enzymes. This model describes a family of 2-isopropylmalate synthases found primarily in Bacteria. The homologous families in the Archaea may represent isozymes and/or related enzymes. [Amino acid biosynthesis, Pyruvate family]