Changes in active site geometry through non active site C95A mutation in tethered HIV-1 protease heterodimer

Insights into a mutation-assisted lateral drug escape mechanism from the HIV-1 protease active site.

We provide insight into the first stages of a kinetic mechanism of lateral drug expulsion from the active site of HIV-1 protease, by conducting all atom molecular dynamics simulations with explicit solvent over a time scale of 24 ns for saquinavir bound to the wildtype, G48V, L90M and G48V/L90M mutant proteases. We find a consistent escape mechanism associated with the G48V mutation. First, inc...

Active - site Mutation in Hypomaturation Amelogenesis Imperfecta

Active Site-directed Inhibition by Optically Pure Epoxyalkyl Cellobiosides Reveals Differences in Active Site Geometry

1,31,4-@-~-Glucan 4-glucanohydrolases (EC 3.2.1.73) from Bacillus subtilis and barley (Hordeum vulgare) with identical substrate specificities but unrelated primary structures have been probed with (R,S)epoxyalkyl (-propyl, -butyl, -pentyl) 8-cellobiosides and with optically pure (3s)and (3R)-3,4-cellobiosides as active site-directed inhibitors. The optimal aglycon length for inactivation diff...

Comparing the accumulation of active- and nonactive-site mutations in the HIV-1 protease.

Protease inhibitor resistance still poses one of the greatest challenges in treating HIV. To better design inhibitors able to target resistant proteases, a deeper understanding is needed of the effects of accumulating mutations and the contributions of active- and nonactive-site mutations to the resistance. We have engineered a series of variants containing the nonactive-site mutations M46I and...

Active site geometry of glucose-1-phosphate uridylyltransferase.

Glucose-1-phosphate uridylyltransferase, or UGPase, catalyzes the production of UDP-glucose from glucose-1-phosphate and UTP. Because of the biological role of UDP-glucose in glycogen synthesis and in the formation of glycolipids, glycoproteins, and proteoglycans, the enzyme is widespread in nature. Recently this laboratory reported the three-dimensional structure of UGPase from Escherichia col...