1fga
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REFINEMENT OF THE STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION AND ANALYSIS OF PRESUMED HEPARIN BINDING SITES BY SELENATE SUBSTITUTION
OverviewOverview
The three-dimensional structure of human basic fibroblast growth factor, has been refined to a crystallographic residual of 16.1% at 1.6 A, resolution. The structure has a Kunitz-type fold and is composed of 12, antiparallel beta-strands, 6 of which form a beta-barrel. One bound, sulfate ion has been identified in the model, hydrogen bonded to the side, chains of Asn 27, Arg 120, and Lys 125. The side chain of Arg 120 has two, conformations, both of which permit hydrogen bonds to the sulfate. This, sulfate binding site has been suggested as the binding site for heparin, (Eriksson, A.E., Cousens, L.S., Weaver, L.H., & Matthews, B.W., 1991, Proc. Natl. Acad. Sci. USA 88, 3441-3445). Two beta-mercaptoethanol (BME), molecules are also included in the model, each forming a disulfide bond to, the S gamma atoms of Cys 69 and Cys 92, respectively. The side chain of, Cys 92 has two conformations of which only one can bind BME. Therefore the, BME molecule is half occupied at this site. The locations of possible, sulfate binding sites on the protein were examined by replacing the, ammonium sulfate in the crystallization medium with ammonium selenate., Diffraction data were measured to 2.2 A resolution and the structure, refined to an R-factor of 13.8%. The binding of the more electron-dense, selenate ion was identified at two positions. One position was identical, to the sulfate binding site identified previously. The second selenate, binding site, which is of lower occupancy, is situated 5.6 A from the, first. This ion is hydrogen bonded by the side chain of Lys 135 and Arg, 120. Thus the side chain of Arg 120 binds two selenate ions, simultaneously. It is suggested that the observed second selenate binding, site should also be considered as a possible binding site for heparin, or, that both selenate binding sites might simultaneously contribute to the, binding of heparin.
DiseaseDisease
Known diseases associated with this structure: Hypophosphatemic rickets, autosomal dominant OMIM:[605380], Osteomalacia, tumor-induced OMIM:[605380], Tumoral calcinosis, hyperphosphatemic, familial OMIM:[605380]
About this StructureAbout this Structure
1FGA is a Single protein structure of sequence from Homo sapiens with SE4 and BME as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Refinement of the structure of human basic fibroblast growth factor at 1.6 A resolution and analysis of presumed heparin binding sites by selenate substitution., Eriksson AE, Cousens LS, Matthews BW, Protein Sci. 1993 Aug;2(8):1274-84. PMID:7691311
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