1T1R

Crystal Structure of the Reductoisomerase Complexed with a Bisphosphonate

Summary for 1T1R

• Entry DOI: 10.2210/pdb1t1r/pdb
• Related: 1JVS 1T1S
• Descriptor: 1-deoxy-D-xylulose 5-phosphate reductoisomerase, SULFATE ION, [(ISOQUINOLIN-1-YLAMINO)-PHOSPHONO-METHYL]-PHOSPHONIC ACID, ... (4 entities in total)
• Functional Keywords: three domains, oxidoreductase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 87543.91

Authors

Yajima, S.,Hara, K.,Sanders, J.M.,Yin, F.,Ohsawa, K.,Wiesner, J.,Jomaa, H.,Oldfield, E. (deposition date: 2004-04-17, release date: 2004-09-14, Last modification date: 2024-03-13)

Primary citation

Yajima, S.,Hara, K.,Sanders, J.M.,Yin, F.,Ohsawa, K.,Wiesner, J.,Jomaa, H.,Oldfield, E.
Crystallographic Structures of Two Bisphosphonate:1-Deoxyxylulose-5-Phosphate Reductoisomerase Complexes
J.Am.Chem.Soc., 126:10824-10825, 2004

PubMed Abstract: 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.

PubMed: 15339150
DOI: 10.1021/ja040126m

Experimental method

X-RAY DIFFRACTION (2.3 Å)