Structural comparison of the catalytic domain of AFL with a homologous lipase from Bacillus subtilis reveals an opposite substrate binding orientation in the two enzymes.
All synthesized compounds were also subjected for molecular docking study with pf KASI/II enzyme to analyze their binding orientation in the active site of the enzyme.
This difference in binding orientation in the absence of co-binding peptide could occur from three possibilities: First, the X-ray crystals contain peptides so the actual binding mode of abacavir without peptide is unknown.
When the crystal structures of (R -flurbiprofen and 3a bound to mCOX-2 aR -flurbiprofene two profens hand the same general binding orientation in the mCOX-2 active site (0.24 Å rmsd, Figure S2).
However, from our analysis of homology models, it appears likely that TxIA(A10L) adopts the same orientation in α3β2 nAChRs as seen in our crystal structure, whereas it may adopt a PnIA-like binding orientation in the α7 nAChR binding pocket.
This is consistent with a previous study in which pairs of domains that were observed to interact both inter- and intramolecularly, which included several fusions, were shown to conserve their binding orientations in most cases (Kim et al., 2006b).
2ROX) indicates a binding orientation in which the alanyl moiety of T4 facilitates hydrogen bonding interactions with Lys15 and Glu54, and the phenol is oriented towards Ser117 and Thr119 (Wojtczak et al. 1996).
The tight conformation of BLM when bound to metal likely precludes the correct binding orientation in BlmB necessary for catalysis and prevents BlmB from pulling apart the tightly chelated nitrogen atoms.
One key goal in this project was to determine which residue(s) controlled substrate binding orientation in OYE 2.6.
Steric clashes, loss of electrostatic stabilization between an active-site arginine (Arg305) and the phosphonate analog, and a 180° flip of the hexose moiety account for the differences in the binding orientations of the isosteric phosphonate analog and the physiological substrate.
