|1jdj, resolution 2.20Å ()|
CRYSTAL STRUCTURE OF LEISHMANIA MEXICANA GLYCEROL-3-PHOSPHATE DEHYDROGENASE IN COMPLEX WITH 2-FLUORO-6-CHLOROPURINE
Pathogenic protozoa such as Trypanosome and Leishmania species cause tremendous suffering worldwide. Because of their dependence on glycolysis for energy, the glycolytic enzymes of these organisms, including glycerol-3-phosphate dehydrogenase (GPDH), are considered attractive drug targets. Using the adenine part of NAD as a lead compound, several 2,6-disubstituted purines were synthesized as inhibitors of Leishmania mexicana GPDH (LmGPDH). The electron densities for the inhibitor 2-bromo-6-chloro-purine bound to LmGPDH using a "conventional" wavelength around 1 A displayed a quasisymmetric shape. The anomalous signals from data collected at 1.77 A clearly indicated the positions of the halogen atoms and revealed the multiple binding modes of this inhibitor. Intriguing differences in the observed binding modes of the inhibitor between very similarly prepared crystals illustrate the possibility of crystal-to-crystal variations in protein-ligand complex structures.
Anomalous differences of light elements in determining precise binding modes of ligands to glycerol-3-phosphate dehydrogenase., Choe J, Suresh S, Wisedchaisri G, Kennedy KJ, Gelb MH, Hol WG, Chem Biol. 2002 Nov;9(11):1189-97. PMID:12445769
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Choe J, Suresh S, Wisedchaisri G, Kennedy KJ, Gelb MH, Hol WG. Anomalous differences of light elements in determining precise binding modes of ligands to glycerol-3-phosphate dehydrogenase. Chem Biol. 2002 Nov;9(11):1189-97. PMID:12445769