1MKX

THE CO-CRYSTAL STRUCTURE OF UNLIGANDED BOVINE ALPHA-THROMBIN AND PRETHROMBIN-2: MOVEMENT OF THE YPPW SEGMENT AND ACTIVE SITE RESIDUES UPON LIGAND BINDING

Summary for 1MKX

• Entry DOI: 10.2210/pdb1mkx/pdb
• Descriptor: ALPHA-THROMBIN, PRETHROMBIN-2, ... (4 entities in total)
• Functional Keywords: complex (blood coagulation-proenzyme), thrombin, prethrombin-2, plasma, serine protease, complex (blood coagulation-proenzyme) complex, complex (blood coagulation/proenzyme)
• Biological source: Bos taurus (cattle); More
• Cellular location: Secreted, extracellular space: P00735 P00735 P00735
• Total number of polymer chains: 3
• Total formula weight: 70997.29

Authors

Malkowski, M.G.,Edwards, B.F.P. (deposition date: 1997-03-13, release date: 1997-07-07, Last modification date: 2024-10-23)

Primary citation

Malkowski, M.G.,Martin, P.D.,Guzik, J.C.,Edwards, B.F.
The co-crystal structure of unliganded bovine alpha-thrombin and prethrombin-2: movement of the Tyr-Pro-Pro-Trp segment and active site residues upon ligand binding.
Protein Sci., 6:1438-1448, 1997

PubMed Abstract: Unliganded bovine alpha-thrombin and prethrombin-2 have been co-crystallized, in space group P21212, using either ammonium sulfate or polyethylene glycol 2000 (PEG2K), and their structures determined at 2.2 A and 2.3 A, respectively. Initial phases were determined by molecular replacement and refined using XPLOR to final R factors of 0.187 (Rfree = 0.255) and 0.190 (Rfree = 0.282) for the salt and PEG2K models, respectively. The apo-enzyme form of bovine alpha-thrombin shows dramatic shifts in placement for the Tyr-Pro-Pro-Trp segment, for Glu-192, and for the catalytic residues His-57 and Ser-195, when compared to 4 thrombin complexes representing different states of catalysis, namely (1) the Michaelis complex (residues 7-19 of fibrinogen A alpha with a non-cleavable scissile bond), (2) enzyme-inhibitor complex (D-Phe-Pro-Arg chloromethylketone), (3) enzyme product complex (residues 7-16 of fibrinopeptide A), and (4) the exosite complex (residues 53-64 of hirudin). The structures of bovine and human prethrombin-2 are generally similar to one another (RMS deviation of 0.68 A) but differ significantly in the Arg-15/Ile-16 cleavage region and in the three activation domains, which are disordered in bovine prethrombin-2, analogous to that seen for trypsinogen.

PubMed: 9232645

Experimental method

X-RAY DIFFRACTION (2.2 Å)