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Growth factor PDB-id
 4fgf
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Protein chain
124 a.a. *
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SO4
BME ×2
Waters ×70

* Residue conservation analysis
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PDB id: 4fgf
Name: Growth factor
Title: 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

Structure:		 Basic fibroblast growth factor. Chain: a. Engineered: yes

Source: 		Homo sapiens. Human. Organism_taxid: 9606

UniProt:
P09038 (FGF2_HUMAN) Pfam  
Seq:
Struc:
Seq: 288 a.a.
Struc: 124 a.a.
Key:    PfamA domain
 Secondary structure  CATH domain

Resolution: 		1.60Å

R-factor: 		0.161

Authors: 		A.E.Eriksson,B.W.Matthews

Key ref:
A.E.Eriksson et al. (1993). 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.. Protein Sci, 2, 1274-1284. [PubMed id: 7691311]

Date: 		26-Feb-93

Release date: 		15-Jul-93
Supersedes: 3fgf
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    Key reference    
 
 
Full text Protein Sci 2:1274-1284 (1993)
PubMed id: 7691311  
 
 
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.
A.E.Eriksson, L.S.Cousens, B.W.Matthews.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. lignmentoftheamioacidsequencesofhbFGFAbrahametal., 1986) (sequencenumberedtocorrespondtobovine bFGF; Eschet l., 1985) andinterleukin(IL)-Ip(Gimenez-Gallegoetal., 1985; Thomas Gimenez-Gallego, 1986) suggested bythecorrespondencebetweentheirthree-dimesionalcrystalstructures(Priestleeal., 1989; Erikssonetal., 1991; thiswork). TesequeneofbovineaFGF is alsoincluded(Gimenez-Gallegoetal., 1985). The50residueswhoseor-carbonsstructurallysu- perimposewith anrmsdiscrepancyof0.52 A areindicatedwithasterisks.ResiduesinbFGFthatareindicatedbythealgorithm ofKabschandSanders (1983) ashavinga&sheetconformationareindicated (0). Thereare IO uch ''&sheet strandsshown inthefigue.Therearetwadditionalsegmnts,indicated 0 . . . ) thatdonot fulfilltheKabschandSanderscriteiafor 0-sheetstrandsbutformthe10thand1lth of the 2 @-strandsthatcomprisetheoverallframework of thebFGFandIL-10struc- tures.Thesesegmentshavebeenrealignedrelative to Erikssonetal. (1991) o nowcompriseresidues 115-117 and 122-127. 		Figure 5.
Fig. 5. Schematicdrawingillustratingthebindingoftwoselenateions tohbFGF.ConventionsasinFigure .
 
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1993, 2, 1274-1284) copyright 1993.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference
  PubMed id Reference
18701883 O.Alsmadi, B.F.Meyer, F.Alkuraya, S.Wakil, F.Alkayal, H.Al-Saud, K.Ramzan, and M.Al-Sayed (2009).
Syndromic congenital sensorineural deafness, microtia and microdontia resulting from a novel homoallelic mutation in fibroblast growth factor 3 (FGF3).
  Eur J Hum Genet, 17, 14-21.  
15954154 H.Yin, and A.D.Hamilton (2005).
Strategies for targeting protein-protein interactions with synthetic agents.
  Angew Chem Int Ed Engl, 44, 4130-4163.  
15924284 Q.Wu, J.Wang, L.Zhang, A.Hong, and J.Ren (2005).
Molecular recognition of basic fibroblast growth factor by polyoxometalates.
  Angew Chem Int Ed Engl, 44, 4048-4052.  
11964252 M.Zamai, C.Hariharan, D.Pines, M.Safran, A.Yayon, V.R.Caiolfa, R.Cohen-Luria, E.Pines, and A.H.Parola (2002).
Nature of Interaction between basic fibroblast growth factor and the antiangiogenic drug 7,7-(carbonyl-bis[imino-N-methyl-4,2-pyrrolecarbonylimino[N-methyl-4,2-pyrrole]-carbonylimino])-bis-(1,3-naphtalene disulfonate). II. Removal of polar interactions affects protein folding.
  Biophys J, 82, 2652-2664.  
10811876 M.M.Young, N.Tang, J.C.Hempel, C.M.Oshiro, E.W.Taylor, I.D.Kuntz, B.W.Gibson, and G.Dollinger (2000).
High throughput protein fold identification by using experimental constraints derived from intramolecular cross-links and mass spectrometry.
  Proc Natl Acad Sci U S A, 97, 5802-5806.  
10666615 Z.Dauter, M.Dauter, and K.R.Rajashankar (2000).
Novel approach to phasing proteins: derivatization by short cryo-soaking with halides.
  Acta Crystallogr D Biol Crystallogr, 56, 232-237.  
10097093 G.Venkataraman, R.Raman, V.Sasisekharan, and R.Sasisekharan (1999).
Molecular characteristics of fibroblast growth factor-fibroblast growth factor receptor-heparin-like glycosaminoglycan complex.
  Proc Natl Acad Sci U S A, 96, 3658-3663.  
10051565 G.Venkataraman, Z.Shriver, J.C.Davis, and R.Sasisekharan (1999).
Fibroblast growth factors 1 and 2 are distinct in oligomerization in the presence of heparin-like glycosaminoglycans.
  Proc Natl Acad Sci U S A, 96, 1892-1897.  
10026256 W.J.LaRochelle, K.Sakaguchi, N.Atabey, H.G.Cheon, Y.Takagi, T.Kinaia, R.M.Day, T.Miki, W.H.Burgess, and D.P.Bottaro (1999).
Heparan sulfate proteoglycan modulates keratinocyte growth factor signaling through interaction with both ligand and receptor.
  Biochemistry, 38, 1765-1771.  
10531488 Y.P.Nieh, and K.Y.Zhang (1999).
A two-dimensional histogram-matching method for protein phase refinement and extension.
  Acta Crystallogr D Biol Crystallogr, 55, 1893-1900.  
9675169 M.Zamai, V.R.Caiolfa, D.Pines, E.Pines, and A.H.Parola (1998).
Nature of interaction between basic fibroblast growth factor and the antiangiogenic drug 7,7-(Carbonyl-bis[imino-N-methyl-4, 2-pyrrolecarbonylimino[N-methyl-4,2-pyrrole]-carbonylimino] )bis-(1, 3-naphthalene disulfonate).
  Biophys J, 75, 672-682.  
9636026 P.J.Kim, K.Sakaguchi, H.Sakamoto, C.Saxinger, R.Day, P.McPhie, J.S.Rubin, and D.P.Bottaro (1998).
Colocalization of heparin and receptor binding sites on keratinocyte growth factor.
  Biochemistry, 37, 8853-8862.  
9125499 F.J.Moy, M.Safran, A.P.Seddon, D.Kitchen, P.Böhlen, D.Aviezer, A.Yayon, and R.Powers (1997).
Properly oriented heparin-decasaccharide-induced dimers are the biologically active form of basic fibroblast growth factor.
  Biochemistry, 36, 4782-4791.  
8780517 A.Krufka, S.Guimond, and A.C.Rapraeger (1996).
Two hierarchies of FGF-2 signaling in heparin: mitogenic stimulation and high-affinity binding/receptor transphosphorylation.
  Biochemistry, 35, 11131-11141.  
8885834 F.J.Moy, A.P.Seddon, P.Böhlen, and R.Powers (1996).
High-resolution solution structure of basic fibroblast growth factor determined by multidimensional heteronuclear magnetic resonance spectroscopy.
  Biochemistry, 35, 13552-13561.
PDB codes: 1bla 1bld
8570646 G.Venkataraman, V.Sasisekharan, A.B.Herr, D.M.Ornitz, G.Waksman, C.L.Cooney, R.Langer, and R.Sasisekharan (1996).
Preferential self-association of basic fibroblast growth factor is stabilized by heparin during receptor dimerization and activation.
  Proc Natl Acad Sci U S A, 93, 845-850.  
8652550 M.Blaber, J.DiSalvo, and K.A.Thomas (1996).
X-ray crystal structure of human acidic fibroblast growth factor.
  Biochemistry, 35, 2086-2094.
PDB codes: 1afg 2afg
7536241 D.B.Volkin, A.M.Verticelli, M.W.Bruner, K.E.Marfia, P.K.Tsai, M.K.Sardana, and C.R.Middaugh (1995).
Deamidation of polyanion-stabilized acidic fibroblast growth factor.
  J Pharm Sci, 84, 7.  
  7507755 P.Pjura, M.Matsumura, W.A.Baase, and B.W.Matthews (1993).
Development of an in vivo method to identify mutants of phage T4 lysozyme of enhanced thermostability.
  Protein Sci, 2, 2217-2225.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.