1NT1

thrombin in complex with selective macrocyclic inhibitor

Summary for 1NT1

• Entry DOI: 10.2210/pdb1nt1/pdb
• Related: 1NM6
• Descriptor: thrombin, Hirudin, (6R,21AS)-17-CHLORO-6-CYCLOHEXYL-2,3,6,7,10,11,19,20-OCTAHYDRO-1H,5H-PYRROLO[1,2-K][1,4,8,11,14]BENZOXATETRAAZA-CYCLOHEPTADECINE-5,8,12,21(9H,13H,21AH)-TETRONE, ... (4 entities in total)
• Functional Keywords: thrombin inhibitor complex, blood clotting-hydrolase inhibitor complex, blood clotting/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space: P00734; Secreted: P28504
• Total number of polymer chains: 2
• Total formula weight: 34961.41

Authors

Nantermet, P.G.,Barrow, J.C.,Newton, C.L.,Pellicore, J.M.,Young, M.,Lewis, S.D.,Lucas, B.J.,Krueger, J.A.,McMasters, D.R.,Yan, Y.,Kuo, L.C.,Vacca, J.P.,Selnick, H.G. (deposition date: 2003-01-28, release date: 2003-09-02, Last modification date: 2024-10-16)

Primary citation

Nantermet, P.G.,Barrow, J.C.,Newton, C.L.,Pellicore, J.M.,Young, M.,Lewis, S.D.,Lucas, B.J.,Krueger, J.A.,McMasters, D.R.,Yan, Y.,Kuo, L.C.,Vacca, J.P.,Selnick, H.G.
Design and synthesis of potent and selective macrocyclic thrombin inhibitors
Bioorg.Med.Chem.Lett., 13:2781-2784, 2003

PubMed Abstract: A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity.

PubMed: 12873514
DOI: 10.1016/S0960-894X(03)00506-7

Experimental method

X-RAY DIFFRACTION (2 Å)