Structure and stability of an acidic fibroblast growth factor from Notophthalmus viridescens
by Arunkumar, A. I.; Srisailam, S.; Krishnaswamy, T.; Kumar, S.; Kathir, K. M.; Chi, Y. H.; Wang, H. M.; Chang, G. G.; Chiu, I. M.; Yu, C.
The three-dimensional solution structure of an acidic fibroblast growth factor (nFGF-1) from the newt (Notophthalmus viridescens) is determined using multidimensional NMR techniques. Complete assignment of all the atoms (H-1, N-15, and C-13) has been achieved using a variety of triple resonance experiments. 50 structures were calculated using hybrid distance geometry-dynamical simulated annealing technique with a total of 1359 constraints. The atomic root mean square distribution for the backbone atoms in the structured region is 0.60 Angstrom. The secondary structural elements include 12 beta-strands arranged antiparallely into a beta-barrel structure. The protein (nFGF-1) exists in a monomeric state upon binding to the ligand, sucrose octa sulfate (SOS), in a stoichiometric ratio of 1:1. The SOS binding site consists of a dense cluster of positively charged residues located at the C-terminal end of the molecule. The conformational stabilities of nFGF-1 and its structural and functional homologue from the human source (hFGF-1) are drastically different. The differential stabilities of nFGF-1 and hFGF-1 are attributed to the differences in the number of hydrogen bonds and the presence of solvent inaccessible cavities in the two proteins.
- Journal
- Journal of Biological Chemistry
- Volume
- 277
- Issue
- 48
- Year
- 2002
- Start Page
- 46424-46432
- URL
- https://dx.doi.org/10.1074/jbc.m207814200
- ISBN/ISSN
- 1083-351X; 0021-9258
- DOI
- 10.1074/jbc.m207814200