X-ray crystallographic
structures of the pocket conformation of
tankyrase2-olaparib (TNKS2–OLA) complex, tankyrase2-XAV939
(TNKS2–XAV) complex, and unbound-tankyrase2 (apo-TNKS2). The
X-ray crystallographic structures of pocket conformations of the TNKS2–OLA
complex, the TNKS2–XAV complex, and apo-TNKS2 are shown in
left, center, and right panels, respectively. Top figures show the
conformations of the ligand binding pockets. Several key residues
(Gly1032, Phe1035, His1048, Tyr1050, Tyr1060, Ser1068, and Tyr1071)
are shown using a green stick model. The α3 helix, D-loop, and
G-loop regions are shown in magenta. The bound ligands are shown using
a ball-and-stick model in cyan. The black dotted lines indicate the
distance between the geometric center of the Tyr1050 phenyl ring and
that of the Tyr1070 (the ring distance of Tyr1050–Tyr1071)
(Å) and the minimum distances between Phe1035 and His1048 (the
minimum distance of Phe1035–His1048) (Å). The middle figures
show the ligand binding pockets depicted using a molecular surface
representation. The hydrophilic and lipophilic regions are drawn in
purple and green, respectively. The bottom figures illustrate the
structural formula of each ligand. The black dotted lines with numerals
represent the distances of hydrogen bonds between the ligand and the
amino acids in the binding pocket. AD, adenosine subsite; NI, nicotinamide
subsite.