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Proc Natl Acad Sci U S A. Apr 15, 1991; 88(8): 3441–3445.
PMCID: PMC51463

Three-dimensional structure of human basic fibroblast growth factor.

Abstract

The three-dimensional structure of human basic fibroblast growth factor (bFGF) has been determined by x-ray crystallography and refined to a crystallographic residual of 17.4% at 2.2-A resolution. The structure was initially solved at a nominal resolution of 2.8 A by multiple isomorphous replacement using three heavy-atom derivatives. Although the map clearly showed the overall fold of the molecule, electron density was not observed for the first 19 amino-terminal and the last 3 carboxyl-terminal amino acids, suggesting that they are disordered. The bFGF crystals were grown from 2.0 M ammonium sulfate at pH 8.1 in space group P1 with cell dimensions a = 30.9 A, b = 33.4 A, c = 35.9 A, alpha = 59.5 degrees, beta = 72.0 degrees, and gamma = 75.6 degrees. There is one molecule per unit cell and the crystals diffract to spacings beyond 1.9 A. The overall structure of bFGF can be described as a trigonal pyramid with a fold very similar to that reported for interleukin 1 beta, interleukin 1 alpha, and soybean trypsin inhibitor. An apparent sulfate ion is bound within a basic region on the surface of the molecule and has a ligands the main-chain amide of Arg-120 and the side chains of Asn-27, Arg-120, and Lys-125. This is suggested as the presumed binding site for heparin. Residues 106-115, which are presumed to bind to the bFGF receptor [Baird, A., Schubert, D., Ling, N. & Guillemin, R. (1988) Proc. Natl. Acad. Sci. USA 85, 2324-2328], include an irregular loop that extends somewhat from the surface of the protein and is about 25 A from the presumed heparin binding site. The backbone structure of this putative receptor-binding loop is very similar, although not identical, to the corresponding region of interleukin 1 beta.

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