title: Do the crystallographic forms of prethrombin-2 revert to a single form in solution?
abstract: It has been earlier established (Pozzi et al. Biochemistry 50 (2011) 10195-10202) that prethrombin-2 crystallizes into two similar but distinct forms: a collapsed form and an alternative form. We employed long molecular dynamics (MD) simulations for these two forms to obtain solvent-equilibrated forms. We find that, at 200ns, the simulated solution collapsed form is quite similar to the X-ray crystal collapsed form, while the simulated solution alternative form deviates from the X-ray crystal alternative form as well as from the solution collapsed form. A detailed structural analysis suggests that the fluctuation of the 140s-loop, in cross-talk with the 220s-loop, may alter the conformation of the W215-E217 segment near the nascent thrombin active site. A rationale is provided for the manner in which interactions of prethrombin-2 with FVa may affect the equilibrium between the two forms of prethrombin-2.
authors.affiliation: Department of Physics, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Sangwook
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Joong-Youn
authors.initials: JY
authors.lastname: Shim
authors.affiliation: Department of Chemistry, Pohang University of Science and Technology, POSTECH, Pohang 790-784, Republic of Korea.
authors.forename: Chang Jun
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: pedersen@ad.unc.edu.
authors.forename: Lee G
authors.initials: LG
authors.lastname: Pedersen
mesh_terms: D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011487:Protein Conformation; D011516:Prothrombin / Q000737:chemistry*; D012996:Solutions
chemical_list: D012996:Solutions; D011516:Prothrombin; C012007:prethrombins
keywords: Coagulation cascade; Factor Va; Prethrombin-2; Prothrombin activation; Thrombin