The natural product swainsonine is known to be a versatile glycosidase inhibitor having previously been used to study the active center of the. ❋ Michael D. L. Suits Et Al. (2010)
(D) schematic diagram of the interactions of swainsonine (shown in panel C) with H-bonds > ❋ Michael D. L. Suits Et Al. (2010)
S. pyogenes bound to the therapeutically important inhibitor swainsonine. ❋ Michael D. L. Suits Et Al. (2010)
Diffraction data for SpGH38 selenomethionine derivative, apo, and swainsonine complex forms were collected at beamlines ID29-2, ID14-2, and ID14-1, respectively, of the European Synchrotron Radiation Facility. ❋ Michael D. L. Suits Et Al. (2010)
Additionally, swainsonine is stabilized through stacking interactions of W18 with the five-membered ring, suggesting that the two aromatic residues contribute to positioning mannose into the correct orientation in the − 1 subsite. ❋ Michael D. L. Suits Et Al. (2010)
These active centre interactions with hydroxyl oxygens 1-3 of swainsonine correspond to analogous interactions between dGMII and hydroxyl groups at positions 4, 3, and 2 of α − mannose in the -1 subsite ❋ Michael D. L. Suits Et Al. (2010)
Subsequently, an inhibited form of SpGH38 in complex with swainsonine was determined at 2.6 Å resolution (discussed below). ❋ Michael D. L. Suits Et Al. (2010)
(A) 3-D topology cartoon (divergent stereo) colored according to domains with swainsonine in ball-and-stick. ❋ Michael D. L. Suits Et Al. (2010)
Arg149 makes a close contact to a swainsonine carbon (indicated with an arrow) of 2.9 Å (spatially equivalent to an H-bond to mannose O6 of the true substrate). doi: 10.1371/journal. pone.0009006.g004 ❋ Michael D. L. Suits Et Al. (2010)
Indeed, the anti-cancer indolizidine alkaloid, swainsonine, is a potent inhibitor of α − mannosidase II and has been shown to reduced metastasis and improved clinical outcomes when used in clinical trials for treatment of colon, breast, and skin cancers ❋ Michael D. L. Suits Et Al. (2010)
Goss PE, Reid CL, Bailey D, Dennis JW (1997) Phase IB clinical trial of the oligosaccharide processing inhibitor swainsonine in patients with advanced malignancies. ❋ Michael D. L. Suits Et Al. (2010)
To confirm the findings, the researcher tested the drug swainsonine, which can inhibit the formation of prions. ❋ Unknown (2010)
α − 1,3 linked disaccharide substrate yielding Catalytic activity of SpGH38 α − mannosidase and inhibition by swainsonine. ❋ Michael D. L. Suits Et Al. (2010)
3-D structure of SpGH38 and its swainsonine complex. ❋ Michael D. L. Suits Et Al. (2010)
v/v polyethylene glycol 6000; for this form appropriate cryo-protection was afforded through increasing the Tacsimate concentration to ~70% v/v. Crystals of the swainsonine complex form were obtained by soaking ❋ Michael D. L. Suits Et Al. (2010)
2 (SeMet derivative and swainsonine complex) crystal systems. ❋ Michael D. L. Suits Et Al. (2010)
The O1 hydroxyl oxygen of swainsonine is stabilized through electrostatic interactions with side chain oxygens of Y574 and D352 and further contributions from D15 and D352 stabilize the O3 and O2 hydroxyl oxygens of swainsonine in the active centre, respectively (schematic diagram in ❋ Michael D. L. Suits Et Al. (2010)
C) The Ki for swainsonine was determined using α − 1,3 mannobiose as substrate with [S] < < Km and [I] straddling the Ki. ❋ Michael D. L. Suits Et Al. (2010)
