3MI2

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

3MI2 の概要

• エントリーDOI: 10.2210/pdb3mi2/pdb
• 関連するPDBエントリー: 2EAW 2P1F 3BGG 3BGJ 3BKO 3BVJ 3G3D 3G3M
• 分子名称: 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)
• 機能のキーワード: ump synthase, orotidine 5'-monophosphate decarboxylase, pyrazofurin monophosphate, lyase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61686.72

構造登録者

Liu, Y.,To, T.,Kotra, L.P.,Pai, E.F. (登録日: 2010-04-09, 公開日: 2010-05-26, 最終更新日: 2024-10-09)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.2 Å)