Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) catalyze the hydrolysis of the neurotransmitter acetylcholine and, thereby, function as coregulators of cholinergic neurotransmission. For both enzymes, hydrolysis takes place near the bottom of a 20 Å deep active site gorge. A number of amino acid residues within the gorge have been identified as important in facilitating efficient ...

We report here our preliminary results on the use of catalytic antibodies as an approach to neutralizing organophosphorus chemical weapons. A first-generation hapten, methyl-alpha-hydroxyphosphinate Ha, was designed to mimic the approach of an incoming water molecule for the hydrolysis of exceedingly toxic methylphosphonothioate VX (1a). A moderate protective activity was first observed on poly...

To increase the pH optimum of glucoamylase (GA), five mutations-S411G, S411A, S411C, S411H and S411D--were designed to destabilize the carboxylate ion form of Glu400, the catalytic base, by removing or weakening the hydrogen bond between Ser411 and Glu400, and thereby raising its pK. The substitution of alanine, histidine and aspartate were also designed to study the additional effects of polar...

The N-terminal nucleophile (Ntn) hydrolases are a superfamily of enzymes specialized in the hydrolytic cleavage of amide bonds. Even though several members of this family are emerging as innovative drug targets for cancer, inflammation, and pain, the processes through which they catalyze amide hydrolysis remains poorly understood. In particular, the catalytic reactions of cysteine Ntn-hydrolase...

Microtubules (MTs) are dynamic structures that are fundamental for cell morphogenesis and motility. MT-associated motors work efficiently to perform their functions. Unlike other motile kinesins, KIF2 catalytically depolymerizes MTs from the peeled protofilament end during ATP hydrolysis. However, the detailed mechanism by which KIF2 drives processive MT depolymerization remains unknown. To elu...

Cellulolytic enzymes consist of a catalytic domain, a linking peptide, and a binding domain. The paper describes research on carboxylic acids that have potential as catalytic domains for constructing organic macromolecules for use in cellulose hydrolysis that mimic the action of enzymes. The tested domains consist of the series of mono-, di-, and tricarboxylic acids with a range of pK(a)'s. Thi...

A hybrid Fv fragment of the dinitrophenyl-binding immunoglobulin A (IgA), MPOC315, has been generated by reconstituting a recombinant variable light chain (VL) produced in Escherichia coli with a variable heavy chain (VH) derived from the antibody. The Tyr34 residue of VL was substituted by His in order to introduce a catalytic imidazole into the combining site for the ester hydrolysis. The His...

A significant contribution to displacement of fossil petroleum utilization can be made through the use of renewable waste and byproduct material for commodity chemical production. One such opportunity is lactose recovered from cheese whey. Several routes for use have been considered. A process involving catalytic hydrolysis of the lactose, catalytic hydrogenation to produce the sugar alcohols, ...

The dependence of the catalytic activities of α-chymotrypsin on the concentration of organic cosolvents (acetonitrile, dimethyl sulfoxide, dimethyl formamide, ethylene glycol, methanol, ethanol, propan-2-ol and tert-butanol) in mixed aqueous media has been studied towards hydrolysis of p-nitrophenyl acetate and p-nitrophenyl benzoate using cetyltriphenylphosphonium bromide surfactant at pH 7.75...

P-glycoprotein (Pgp) is an ABC transporter responsible for the ATP-dependent efflux of chemotherapeutic compounds from multidrug resistant cancer cells. Better understanding of the molecular mechanism of Pgp-mediated transport could promote rational drug design to circumvent multidrug resistance. By measuring drug binding affinity and reactivity to a conformation-sensitive antibody we show here...