TY - JOUR
T1 - Anomalous differences of light elements in determining precise binding modes of ligands to glycerol-3-phosphate dehydrogenase
AU - Choe, Jungwoo
AU - Suresh, Stephen
AU - Wisedchaisri, Goragot
AU - Kennedy, Kevin J.
AU - Gelb, Michael H.
AU - Hol, Wim G.J.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - 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 Å displayed a quasisymmetric shape. The anomalous signals from data collected at 1.77 Å 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.
AB - 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 Å displayed a quasisymmetric shape. The anomalous signals from data collected at 1.77 Å 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.
UR - http://www.scopus.com/inward/record.url?scp=0036851224&partnerID=8YFLogxK
U2 - 10.1016/S1074-5521(02)00243-0
DO - 10.1016/S1074-5521(02)00243-0
M3 - Article
C2 - 12445769
AN - SCOPUS:0036851224
SN - 1074-5521
VL - 9
SP - 1189
EP - 1197
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 11
ER -