Connected cavity structure enables prenyl elongation across the dimer interface in mutated geranylfarnesyl diphosphate synthase from Methanosarcina mazei

The mechanism for product chain-length determination of geranylfarnesyl diphosphate synthase from the methanogenic archaeon Methanosarcina mazei was investigated by constructing mutants based on structural information. Among the mutants, in which each of the bulky residues that constitute the bottom of the product-accommodating cavity was replaced with alanine, those having mutations on an α-helix existing at the subunit interface yielded longer products. In particular, replacement of isoleucine 112 on the α-helix greatly elongated the product chain-length, probably by connecting the reaction cavities of two subunits across the dimer interface.

► Geranylfarnesyl diphosphate synthase from Methanosarcina mazei was mutated.
► Mutations at the homodimeric subunit interface affected product specificity.
► Replacement of Ile112 with alanine greatly elongated the product chain-length.
► The model of the mutant suggested that its cavity is connected between the subunits.
► The connected cavity might allow prenyl elongation across the dimer interface.