1FV9

Crystal structure of human microurokinase in complex with 2-amino-5-hydroxy-benzimidazole

1FV9 の概要

• エントリーDOI: 10.2210/pdb1fv9/pdb
• 分子名称: UROKINASE, SULFATE ION, 2-AMINO-5-HYDROXY-BENZIMIDAZOLE (3 entities in total)
• 機能のキーワード: plasminogen activation, blood clotting
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P00749
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27835.64

構造登録者

Nienaber, V. (登録日: 2000-09-19, 公開日: 2000-10-18, 最終更新日: 2024-11-13)

主引用文献

Hajduk, P.J.,Boyd, S.,Nettesheim, D.,Nienaber, V.,Severin, J.,Smith, R.,Davidson, D.,Rockway, T.,Fesik, S.W.
Identification of novel inhibitors of urokinase via NMR-based screening.
J.Med.Chem., 43:3862-3866, 2000

PubMed Abstract: Using an NMR-based screen, a novel class of urokinase inhibitors were identified that contain a 2-aminobenzimidazole moiety. The inhibitory potency of this family of inhibitors is similar to that of inhibitors containing a guanidine or amidine group. However, unlike previously described guanidino- or amidino-based inhibitors which have pK(a) values greater than 9.0, urokinase inhibitors containing a 2-aminobenzimidazole have pK(a) values of 7.5. Thus, 2-aminobenzimidazoles may have improved pharmacokinetic properties which could increase the bioavailability of inhibitors which contain this moiety. A crystal structure of one of the lead inhibitors, 2-amino-5-hydroxybenzimidazole, complexed with urokinase reveals the electrostatic and hydrophobic interactions that stabilize complex formation and suggests nearby subsites that may be accessed to increase the potency of this new series of urokinase inhibitors.

PubMed: 11052791
DOI: 10.1021/jm0002228

実験手法

X-RAY DIFFRACTION (3 Å)