Mutagenesis of the crystal contact of acidic fibroblast growth factor

Honjo, Eijiro; Tamada, Taro; Adachi, Motoyasu; Kuroki, Ryota; Meher, A.*; Blaber, M.*

We attempt to improve a crystal contact of human acidic fibroblast growth factor (haFGF1) to control the crystal growth because haFGF crystallizes only as a thin-plate form. X-ray crystal analysis of haFGF showed that side chain Glu81, located at a crystal contact between haFGF molecules related by crystallographic symmetry, were in close proximity, suggesting that charge-repulsion may disrupt suitable crystal-packing interaction. To investigate whether the Glu residue affects crystal packing, we constructed haFGF mutants. Although crystals of Ala, Val and Leu mutants were grown as a thin-plate form by the same precipitant (formate) as wild type, crystals of Ser and Thr mutants were grown as a more bulky form. X-ray structural analysis of Ser and Thr mutants determined at 1.5 resolution revealed that hydroxyl groups of Ser and Thr were linked by hydrogen bonds mediated by formate used as a precipitant.