TY - DATA T1 - Crystallographic Structures of Two Bisphosphonate:1-Deoxyxylulose-5-Phosphate Reductoisomerase Complexes PY - 2004/09/08 AU - Shunsuke Yajima AU - Kodai Hara AU - John M. Sanders AU - Fenglin Yin AU - Kanju Ohsawa AU - Jochen Wiesner AU - Hassan Jomaa AU - Eric Oldfield UR - https://acs.figshare.com/articles/journal_contribution/Crystallographic_Structures_of_Two_Bisphosphonate_1_Deoxyxylulose_5_Phosphate_Reductoisomerase_Complexes/3325696 DO - 10.1021/ja040126m.s001 L4 - https://ndownloader.figshare.com/files/5164480 KW - bisphosphonates bind KW - sulfate ion KW - Crystallographic Structures KW - crystal structures KW - antimalarial drugs KW - phosphonate groups KW - EC KW - antiinfective agents KW - fosmidomycin binding site KW - DXR inhibitors KW - carboxylic acid groups N2 - We have obtained the single-crystal X-ray crystallographic structures of the bisphosphonates [(1-isoquinolinylamino)methylene]-1,1-bisphosphonate and [[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate, bound to the enzyme 1-deoxyxylulose-5-phosphate reductoisomerase (DXR, EC 1.1.1.267, also known as 2-C-methyl-d-erythritol-4-phosphate synthase), an important target for the development of antimalarial drugs. Our results indicate that both bisphosphonates bind into the fosmidomycin binding site. The aromatic groups are in a shallow hydrophobic pocket, and the phosphonate groups are involved in electrostatic interactions with Mg2+ or a cluster of carboxylic acid groups and lysine while the fosmidomycin phosphonate-binding site is occupied by a sulfate ion (as also observed in the DXR/NADP+ structure). The availability of these two new crystal structures opens up the possibility of the further development of bisphosphonates and related systems as DXR inhibitors and, potentially, as antiinfective agents. ER -