3E6P

Crystal structure of human meizothrombin desF1

Summary for 3E6P

• Entry DOI: 10.2210/pdb3e6p/pdb
• Related: 1A0H
• Descriptor: Prothrombin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, SULFATE ION, ... (7 entities in total)
• Functional Keywords: thrombin, meizothrombin, allostery, linkage, na+ binding, acute phase, blood coagulation, cleavage on pair of basic residues, disease mutation, gamma-carboxyglutamic acid, glycoprotein, hydrolase, kringle, protease, secreted, serine protease, zymogen
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 48328.36

Authors

Papaconstantinou, M.E.,Gandhi, P.,Chen, Z.,Bah, A.,Di Cera, E. (deposition date: 2008-08-15, release date: 2008-11-18, Last modification date: 2024-10-30)

Primary citation

Papaconstantinou, M.E.,Gandhi, P.S.,Chen, Z.,Bah, A.,Di Cera, E.
Na(+) binding to meizothrombin desF1.
Cell.Mol.Life Sci., 65:3688-3697, 2008

PubMed Abstract: Meizothrombin is the physiologically active intermediate generated by a single cleavage of prothrombin at R320 to separate the A and B chains. Recent evidence has suggested that meizothrombin, like thrombin, is a Na(+)-activated enzyme. In this study we present the first X-ray crystal structure of human meizothrombin desF1 solved in the presence of the active site inhibitor PPACK at 2.1 A resolution. The structure reveals a Na(+) binding site whose architecture is practically identical to that of human thrombin. Stopped-flow measurements of Na(+) binding to meizothrombin desF1 document a slow phase of fluorescence change with a k(obs) decreasing hyperbolically with increasing [Na(+)], consistent with the existence of three conformations in equilibrium, E*, E and E:Na(+), as for human thrombin. Evidence that meizothrombin exists in multiple conformations provides valuable new information for studies of the mechanism of prothrombin activation.

PubMed: 18854941
DOI: 10.1007/s00018-008-8502-7

Experimental method

X-RAY DIFFRACTION (2.1 Å)