title: Structural determinants for the inhibitory ligands of orotidine-5'-monophosphate decarboxylase.
abstract: In recent years, orotidine-5'-monophosphate decarboxylase (ODCase) has gained renewed attention as a drug target. As a part of continuing efforts to design novel inhibitors of ODCase, we undertook a comprehensive study of potent, structurally diverse ligands of ODCase and analyzed their structural interactions in the active site of ODCase. These ligands comprise of pyrazole or pyrimidine nucleotides including the mononucleotide derivatives of pyrazofurin, barbiturate ribonucleoside, and 5-cyanouridine, as well as, in a computational approach, 1,4-dihydropyridine-based non-nucleoside inhibitors such as nifedipine and nimodipine. All these ligands bind in the active site of ODCase exhibiting distinct interactions paving the way to design novel inhibitors against this interesting enzyme. We propose an empirical model for the ligand structure for rational modifications in new drug design and potentially new lead structures.
authors.affiliation: Division of Cell & Molecular Biology, University Health Network, Toronto, ON, Canada.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Meza-Avina
authors.forename: Lianhu
authors.initials: L
authors.lastname: Wei
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Ewa
authors.initials: E
authors.lastname: Poduch
authors.forename: Angelica M
authors.initials: AM
authors.lastname: Bello
authors.forename: Ram K
authors.initials: RK
authors.lastname: Mishra
authors.forename: Emil F
authors.initials: EF
authors.lastname: Pai
authors.forename: Lakshmi P
authors.initials: LP
authors.lastname: Kotra
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D009964:Orotidine-5'-Phosphate Decarboxylase
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