3K65

Crystal Structure of Prethombin-2/Fragment-2 Complex

Summary for 3K65

• Entry DOI: 10.2210/pdb3k65/pdb
• Related: 1HAG 2HPQ 3E6P
• Descriptor: Prothrombin, 1,4-BUTANEDIOL, ... (4 entities in total)
• Functional Keywords: prothrombin, coagulation, zymogen, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted, extracellular space: P00734 P00734
• Total number of polymer chains: 2
• Total formula weight: 48191.22

Authors

Adams, T.E.,Huntington, J.A. (deposition date: 2009-10-08, release date: 2010-09-29, Last modification date: 2023-09-06)

Primary citation

Adams, T.E.,Huntington, J.A.
Structural transitions during prothrombin activation: On the importance of fragment 2.
Biochimie, 122:235-242, 2016

PubMed Abstract: Prothrombin is activated to thrombin by the prothrombinase complex through sequential cleavage at two distinct sites. This occurs at sites of vascular injury in a highly regulated cascade of serine protease and cofactor activation, where activated platelets provide a suitable surface for protease/cofactor/substrate assembly. The precise structural and conformational changes undergone during the transition from prothrombin to thrombin have been studied for decades, and several structures of prothrombin fragments along the activation pathway have been solved. Here we present a new structure analyzed in context of other recent structures and biochemical studies. What emerges is an unexpected mechanism that involves a change in the mode of binding of the F2 domain (fragment 2) on the catalytic domain after cleavage at Arg320, and a subsequent reorientation of the linker between the F2 and catalytic domain to present the Arg271 site for cleavage.

PubMed: 26365066
DOI: 10.1016/j.biochi.2015.09.013

Experimental method

X-RAY DIFFRACTION (1.85 Å)