title: The NMR solution structure of recombinant RGD-hirudin.
abstract: The solution structure of a new recombinant RGD-hirudin, which has the activities of anti-thrombin and anti-platelet aggregation, was determined by (1)H nuclear magnetic resonance spectroscopy and compared with the conformations of recombinant wild-type hirudin and hirudin (variant 2, Lys47) of the hirudin thrombin complex. On the basis of total 1284 distance and dihedral angle constraints derived from a series of NMR spectra, 20 conformers were computed with ARIA/CNS programs. The structure of residues 3-30 and 37-48 form a molecular core with two antiparallel beta-sheets as the other two hirudins. However, significant differences were found in the surface electrostatic charge distributions among the three hirudins, especially in the RGD segment of recombinant RGD-hirudin. This difference may be greatly beneficial to its additional function of anti-platelet aggregation. The difference in extended C-terminal makes its both ionic and hydrophobic interactions with the fibrinogen recognition exosite of thrombin more effective.
authors.affiliation: Center of Analysis and Measurement, Fudan University, Shanghai 200433, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Song
authors.forename: Wei
authors.initials: W
authors.lastname: Mo
authors.forename: Xingang
authors.initials: X
authors.lastname: Liu
authors.forename: Lina
authors.initials: L
authors.lastname: Zhu
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yan
authors.forename: Houyan
authors.initials: H
authors.lastname: Song
authors.forename: Linsen
authors.initials: L
authors.lastname: Dai
mesh_terms: D003198:Computer Simulation; D006629:Hirudins / Q000737:chemistry* / Q000648:ultrastructure*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010446:Peptide Fragments / Q000737:chemistry* / Q000648:ultrastructure*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C069897:hirudin (53-64), RGD-