Proposed mechanism
of conformational changes of ligand-binding
pocket on OLA binding. Four conformations (NI-closed/AD-closed (1),
NI-open/AD-closed (1′ and 2), NI-open/AD-semi-open (3), and
NI-open/AD-open (4) forms) of the ligand binding pocket of TNKS2 are
shown. The dotted box indicates the conformational change between
the NI-closed/AD-closed (1) and NI-open/AD-closed (1′) forms
of apo-TNKS2. The black arrows indicate the main conformational change
pathway of TNKS2 upon OLA binding. The ligand binding pocket is depicted
using molecular surface representations. IPA molecule shown in the
ball-and-stick model is in the NI-open/AD-closed (1′) form.
XAV and water molecules shown in ball-and-stick and space-filling
models are in the NI-open/AD-closed (2) and NI-open/AD-semi-open (3)
forms, respectively. The OLA molecule shown in space-filling model
is in the NI-open/AD-open (4) form. The hydrophilic and lipophilic
regions are drawn in orange and blue, respectively.