1z71

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 1z71, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

thrombin and P2 pyridine N-oxide inhibitor complex structure

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

In this study, we have demonstrated that the critical hydrogen bonding motif of the established 3-aminopyrazinone thrombin inhibitors can be effectively mimicked by a 2-aminopyridine N-oxide. As this peptidomimetic core is more resistant toward oxidative metabolism, it also overcomes the metabolic liability associated with the pyrazinones. An optimization study of the P(1) benzylamide delivered the potent thrombin inhibitor 21 (K(i) = 3.2 nM, 2xaPTT = 360 nM), which exhibited good plasma levels and half-life after oral dosing in the dog (C(max) = 2.6 microM, t(1/2) = 4.5 h).

Disease

Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this Structure

1Z71 is a Protein complex structure of sequences from Homo sapiens with as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.

Reference

P2 pyridine N-oxide thrombin inhibitors: a novel peptidomimetic scaffold., Nantermet PG, Burgey CS, Robinson KA, Pellicore JM, Newton CL, Deng JZ, Selnick HG, Lewis SD, Lucas BJ, Krueger JA, Miller-Stein C, White RB, Wong B, McMasters DR, Wallace AA, Lynch JJ Jr, Yan Y, Chen Z, Kuo L, Gardell SJ, Shafer JA, Vacca JP, Lyle TA, Bioorg Med Chem Lett. 2005 Jun 2;15(11):2771-5. PMID:15911253

Page seeded by OCA on Thu Feb 21 16:12:42 2008