1,4-Dideoxy-1,4-imino-D- and L-lyxitol-based inhibitors bind to Golgi α-mannosidase II in different protonation forms.

ABSTRACT: The development of effective inhibitors of Golgi α-mannosidase II (GMII, E.C.3.2.1.114) with minimal off-target effects on phylogenetically-related lysosomal α-mannosidase (LMan, E.C.3.2.1.24) is a complex task due to the complicated structural and chemical properties of their active sites. The pK_a values (and also protonation forms in some cases) of several ionizable amino acids, such as Asp, Glu, His or Arg of enzymes, can be changed upon the binding of the inhibitor. Moreover, GMII and LMan work under different pH conditions. The pK_a calculations on large enzyme-inhibitor complexes and FMO-PIEDA energy decomposition analysis were performed on the structures of selected inhibitors obtained from docking and hybrid QM/MM calculations. Based on the calcul

SUBMITTER: Kona J 

PROVIDER: S-EPMC7614232 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature