The post-translational modification of serine and threonine residues of nucleocytoplasmic proteins with 2-acetamido-2-deoxy-D-glucopyranose (GlcNAc) is a reversible process implicated in multiple cellular processes. The enzyme O-GlcNAcase catalyzes the cleavage of ␤-O-linked GlcNAc (O-GlcNAc) from modified proteins and is a member of the family 84 glycoside hydrolases. The family 20 ␤-hexosaminidases bear no apparent sequence similarity yet are functionally related to O-GlcNAcase because both enzymes cleave terminal GlcNAc residues from glycoconjugates. Lysosomal ␤-hexosaminidase is known to use substrate-assisted catalysis involving the 2-acetamido group of the substrate; however, the catalytic mechanism of human O-GlcNAcase is unknown. By using a series of 4-methylumbelliferyl 2-deoxy-2-N-fluoroacetyl-␤-D-glucopyranoside substrates, Taft-like linear free energy analyses of these enzymes indicates that O-GlcNAcase uses a catalytic mechanism involving anchimeric assistance. Humans have three genes encoding enzymes that cleave terminal N-acetylglucosamine residues from glycoconjugates. The first of these, O-GlcNAcase, 1 is a member of family 84 of glycoside hydrolases that includes enzymes from organisms as diverse as prokaryotic pathogens and humans (1, 2). 2 The substrates of O-GlcNAcase are post-translationally modified glycoproteins bearing the monosaccharide 2-acetamido-2-deoxy-␤-D-glucopyranoside linked to serine or threonine residues (O-GlcNAc) (3-5). This post-translational modification is abundant in mammalian cells (3) and is found on many cellular proteins having a wide range of vital cellular functions, including for example, transcription (6 -9), proteasomal degradation (10), and cellular signaling (11), and is also found on many structural proteins (12)(13)(14). Consistent with the abundance of O-GlcNAc on intracellular proteins, it appears to have roles in the etiology of several disease states, including type II diabetes (11, 15), Alzheimer (13,16,17), and cancer (18). Although O-GlcNAcase was likely isolated earlier on (19,20), an understanding of its biochemical role in acting to cleave O-GlcNAc off from modified serine and threonine residues of proteins waited some 20 years (21). More recently OGlcNAcase has been cloned (23), partially characterized (24), and suggested to have additional activity as a histone acetyltransferase (22). Little, however, is known about the catalytic mechanism of this enzyme.HEXA and HEXB are the two other genes that encode enzymes catalyzing the hydrolytic cleavage of terminal N-acetylglucosamine residues from glycoconjugates. The gene products of HEXA and HEXB predominantly yield two dimeric isozymes. The homodimeric isozyme, hexosaminidase B (␤␤), is composed of two ␤-subunits, and the heterodimeric isozyme, hexosaminidase A (␣␤), is composed of an ␣-and a ␤-subunit. Both of these enzymes are normally localized within the lysosome. The two subunits bear a high level of sequence identity, and both are members of family 20 of glycoside hydrolases. The dysfunction of...

A subtype of PD with functional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor disability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients.

A G-quadruplex (G4) motif was used as a warhead of a proteolysis-targeting chimera (G4-PROTAC) for targeted degradation of a G4-binding protein (RHAU/DHX36), providing a new way to explore G4-protein networks and develop potential therapeutics.

Ceramics of bismuth titanate, Bi 4 Ti 3 O 12 (BIT) and the La-doped series, Bi 4−x La x Ti 3 O 12 (xBLT) with x= 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, and 0.75, have been synthesized by a new sol-gel process based on ethylene glycol. La-doping is found to reduce the temperature of the formation of pure Bi-layer-structured phase from 600°C in BIT and low La-doped xBLT (x=0.1-0.3) to 500°C in high La-doped xBLT (x=0.4-0.75). Increasing the La-content in the xBLT ceramics decreases the contribution of the space charge polarization to the apparent dielectric permittivity. The ceramics of xBLT prepared by this sol-gel route exhibit improved dielectric properties, with a higher room temperature dielectric constant and lower losses up to high temperatures.