3MI2

Crystal structure of human orotidine-5'-monophosphate decarboxylase complexed with pyrazofurin monophosphate

Summary for 3MI2

• Entry DOI: 10.2210/pdb3mi2/pdb
• Related: 2EAW 2P1F 3BGG 3BGJ 3BKO 3BVJ 3G3D 3G3M
• Descriptor: Uridine 5'-monophosphate synthase, (1S)-1,4-anhydro-1-(5-carbamoyl-4-hydroxy-1H-pyrazol-3-yl)-5-O-phosphono-D-ribitol (3 entities in total)
• Functional Keywords: ump synthase, orotidine 5'-monophosphate decarboxylase, pyrazofurin monophosphate, lyase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 61686.72

Authors

Liu, Y.,To, T.,Kotra, L.P.,Pai, E.F. (deposition date: 2010-04-09, release date: 2010-05-26, Last modification date: 2024-10-09)

Primary citation

Meza-Avina, M.E.,Wei, L.,Liu, Y.,Poduch, E.,Bello, A.M.,Mishra, R.K.,Pai, E.F.,Kotra, L.P.
Structural determinants for the inhibitory ligands of orotidine-5'-monophosphate decarboxylase.
Bioorg.Med.Chem., 18:4032-4041, 2010

PubMed 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.

PubMed: 20452222
DOI: 10.1016/j.bmc.2010.04.017

Experimental method

X-RAY DIFFRACTION (1.2 Å)