6C2W
Crystal structure of human prothrombin mutant S101C/A470C
Summary for 6C2W
| Entry DOI | 10.2210/pdb6c2w/pdb |
| Descriptor | Prothrombin, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, MAGNESIUM ION, ... (4 entities in total) |
| Functional Keywords | hydrolase, kringle, enzyme mechanism, coagulation factor, blood clotting |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 134120.52 |
| Authors | Chinnaraj, M.,Chen, Z.,Pelc, L.,Grese, Z.,Bystranowska, D.,Di Cera, E.,Pozzi, N. (deposition date: 2018-01-09, release date: 2018-02-28, Last modification date: 2023-11-15) |
| Primary citation | Chinnaraj, M.,Chen, Z.,Pelc, L.A.,Grese, Z.,Bystranowska, D.,Di Cera, E.,Pozzi, N. Structure of prothrombin in the closed form reveals new details on the mechanism of activation. Sci Rep, 8:2945-2945, 2018 Cited by PubMed Abstract: The clotting factor prothrombin exists in equilibrium between closed and open conformations, but the physiological role of these forms remains unclear. As for other allosteric proteins, elucidation of the linkage between molecular transitions and function is facilitated by reagents stabilized in each of the alternative conformations. The open form of prothrombin has been characterized structurally, but little is known about the architecture of the closed form that predominates in solution under physiological conditions. Using X-ray crystallography and single-molecule FRET, we characterize a prothrombin construct locked in the closed conformation through an engineered disulfide bond. The construct: (i) provides structural validation of the intramolecular collapse of kringle-1 onto the protease domain reported recently; (ii) documents the critical role of the linker connecting kringle-1 to kringle-2 in stabilizing the closed form; and (iii) reveals novel mechanisms to shift the equilibrium toward the open conformation. Together with functional studies, our findings define the role of closed and open conformations in the conversion of prothrombin to thrombin and establish a molecular framework for prothrombin activation that rationalizes existing phenotypes associated with prothrombin mutations and points to new strategies for therapeutic intervention. PubMed: 29440720DOI: 10.1038/s41598-018-21304-1 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (4.12 Å) |
Structure validation
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