Computational Analysis of the Inhibition Mechanism of NOTUM by the ONIOM Method.

Notum is a member of serine hydrolyses that cleaves the palmitoleate moiety from Wingless-related integration site (Wnt) ligands. This enzyme plays crucial functions through modulating the Wnt signaling pathway. Inhibition of Notum carries therapeutic effects against a number of maladies including osteoporosis, cancer, and Alzheimer's disease.

Computational Analysis of Histone Deacetylase 10 Mechanism by the ONIOM Method: A Complementary Approach to X-ray and Kinetics Studies.

Histone deacetylase 10 (HDAC 10) catalyzes deacetylation of N-acetylspermidine into spermidine in the cytosolic region of eukaryotic cells. Inhibition of HDAC 10 has clinical importance in certain types of cancers. Recently, X-ray crystal structures corresponding to the substrate-bound, tetrahedral intermediate-bound, and product-bound enzymes have been resolved using variant forms of humanized HDAC 10.

Mechanistic study of L-6-hydroxynicotine oxidase by DFT and ONIOM methods.

L-6-Hydroxynicotine oxidase (LHNO) is a member of monoamine oxidase (MAO) family and catalyzes conversion of (S)-6-hydroxynicotine to 6-hydroxypseudooxynicotine during bacterial degradation of nicotine. Recent studies indicated that the enzyme catalyzes oxidation of carbon-nitrogen bond instead of previously proposed carbon-carbon bond. Based on kinetics and mutagenesis studies, Asn166, Tyr311, and Lys287 as well as an active site water molecule have roles in the catalysis of the enzyme.

Comparative Computational Approach To Study Enzyme Reactions Using QM and QM-MM Methods.

Choline oxidase catalyzes oxidation of choline into glycine betaine through a two-step reaction pathway employing flavin as the cofactor. On the light of kinetic studies, it is proposed that a hydride ion is transferred from α-carbon of choline/hydrated-betaine aldehyde to the N5 position of flavin in the rate-determining step, which is preceded by deprotonation of hydroxyl group of choline/hydrated-betaine aldehyde to one of the possible basic side chains. Using the crystal structure of glycine betaine-choline oxidase complex, we formulated two computational systems to study the hydride-transfer mechanism including main active-site amino acid side chains, flavin cofactor, and choline as a model system.