Structure and stability of an acidic fibroblast growth factor from Notophthalmus viridescens.
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 ((1)H, (15)N, and (13)C) 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 A. 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.
Arunkumar
Alphonse Ignatius
AI
Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
Srisailam
Sampath
S
Kumar
Thallampuranam Krishnaswamy Suresh
TK
Kathir
Karuppanan Muthusamy
KM
Chi
Ya-Hui
YH
Wang
Han-Min
HM
Chang
Gu-Gang
GG
Chiu
Ing- Ming
I
Yu
Chin
C
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009673:Notophthalmus viridescens / Q000378:metabolism*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D016220:Fibroblast Growth Factor 1