spacer
spacer

PDBsum entry 1afc
Go to PDB code: 
protein ligands links
Growth factor PDB id
1afc

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
(+ 2 more) 127 a.a. *
Ligands
GU4-YYJ ×8
* Residue conservation analysis
PDB id:
1afc
Name: Growth factor
Title: Structural studies of the binding of the anti-ulcer drug sucrose octasulfate to acidic fibroblast growth factor
Structure: Acidic fibroblast growth factor. Chain: a, b, c, d, e, f, g, h. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.70Å     R-factor:   0.204    
Authors: X.Zhu,B.T.Hsu,D.C.Rees
Key ref:
X.Zhu et al. (1993). Structural studies of the binding of the anti-ulcer drug sucrose octasulfate to acidic fibroblast growth factor. Structure, 1, 27-34. PubMed id: 7520817 DOI: 10.1016/0969-2126(93)90006-3
Date:
13-Jul-93     Release date:   31-Oct-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P03968  (FGF1_BOVIN) -  Fibroblast growth factor 1 from Bos taurus
Seq:
Struc: 		155 a.a.
127 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1016/0969-2126(93)90006-3 Structure 1:27-34 (1993)
PubMed id: 7520817  
 
 
Structural studies of the binding of the anti-ulcer drug sucrose octasulfate to acidic fibroblast growth factor.
X.Zhu, B.T.Hsu, D.C.Rees.
 
  ABSTRACT  
 
BACKGROUND: The anti-ulcer drug sucrose octasulfate (SOS) binds to fibroblast growth factors (FGFs), proteins which stimulate the growth and differentiation of several cell types, including stomach epithelial cells. It is believed that SOS stabilizes FGFs against acid denaturation in the stomach, thus enhancing their ability to stimulate healing of ulcerated tissue. SOS binds to the same site on FGF as heparin and other proteoglycans; in vivo, FGF must bind to cell-surface proteoglycans or to heparin before it can interact with FGF receptors and stimulate growth. The details of this process are not understood. RESULTS: We report the crystal structure of a 1:1 complex between acidic FGF (aFGF) and SOS at 2.7 A resolution. SOS binds to a positively charged region of aFGF, largely composed of residues 112-127, and makes contacts primarily with Lys112, Arg116, Lys118, and Arg122. This region is also important in binding heparin. The overall conformation of aFGF is not changed by binding SOS, although the positions of some side chains in the binding site shift by as much as 6 A. CONCLUSION: The SOS-FGF crystal structure is consistent with the model that SOS stabilizes FGF by neutralizing several positively charged residues that would destabilize the native structure by electrostatic repulsion. On the basis of this structure, we provide a model for the complex of heparin with an FGF dimer. Such interactions may facilitate FGF receptor dimerization, which may be important in receptor signaling.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20053992 S.Sarilla, S.Y.Habib, D.V.Kravtsov, A.Matafonov, D.Gailani, and I.M.Verhamme (2010).
Sucrose octasulfate selectively accelerates thrombin inactivation by heparin cofactor II.
  J Biol Chem, 285, 8278-8289.  
18725627 M.Schuksz, M.M.Fuster, J.R.Brown, B.E.Crawford, D.P.Ditto, R.Lawrence, C.A.Glass, L.Wang, Y.Tor, and J.D.Esko (2008).
Surfen, a small molecule antagonist of heparan sulfate.
  Proc Natl Acad Sci U S A, 105, 13075-13080.  
  18540049 N.Kulahin, V.Kiselyov, A.Kochoyan, O.Kristensen, J.S.Kastrup, V.Berezin, E.Bock, and M.Gajhede (2008).
Dimerization effect of sucrose octasulfate on rat FGF1.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 448-452.
PDB code: 2uus
  17277441 N.Kulahin, V.Kiselyov, A.Kochoyan, O.Kristensen, J.S.Kastrup, V.Berezin, E.Bock, and M.Gajhede (2007).
Structure of rat acidic fibroblast growth factor at 1.4 A resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 65-68.
PDB code: 2j3p
17339340 R.Goetz, A.Beenken, O.A.Ibrahimi, J.Kalinina, S.K.Olsen, A.V.Eliseenkova, C.Xu, T.A.Neubert, F.Zhang, R.J.Linhardt, X.Yu, K.E.White, T.Inagaki, S.A.Kliewer, M.Yamamoto, H.Kurosu, Y.Ogawa, M.Kuro-o, B.Lanske, M.S.Razzaque, and M.Mohammadi (2007).
Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members.
  Mol Cell Biol, 27, 3417-3428.
PDB codes: 2p23 2p39
16937240 A.Canales-Mayordomo, R.Fayos, J.Angulo, R.Ojeda, M.Martín-Pastor, P.M.Nieto, M.Martín-Lomas, R.Lozano, G.Giménez-Gallego, and J.Jiménez-Barbero (2006).
Backbone dynamics of a biologically active human FGF-1 monomer, complexed to a hexasaccharide heparin-analogue, by 15N NMR relaxation methods.
  J Biomol NMR, 35, 225-239.  
15863029 M.Mohammadi, S.K.Olsen, and O.A.Ibrahimi (2005).
Structural basis for fibroblast growth factor receptor activation.
  Cytokine Growth Factor Rev, 16, 107-137.  
16175541 S.Cochran, C.P.Li, and I.Bytheway (2005).
An experimental and molecular-modeling study of the binding of linked sulfated tetracyclitols to FGF-1 and FGF-2.
  Chembiochem, 6, 1882-1890.  
14627732 S.R.Brych, J.Kim, T.M.Logan, and M.Blaber (2003).
Accommodation of a highly symmetric core within a symmetric protein superfold.
  Protein Sci, 12, 2704-2718.
PDB codes: 1jy0 1m16 1nzk 1p63
12205097 A.I.Arunkumar, S.Srisailam, T.K.Kumar, K.M.Kathir, Y.H.Chi, H.M.Wang, G.G.Chang, I.Chiu, and C.Yu (2002).
Structure and stability of an acidic fibroblast growth factor from Notophthalmus viridescens.
  J Biol Chem, 277, 46424-46432.
PDB code: 1fmm
11967362 A.I.Arunkumar, T.K.Kumar, K.M.Kathir, S.Srisailam, H.M.Wang, P.S.Leena, Y.H.Chi, H.C.Chen, C.H.Wu, R.T.Wu, G.G.Chang, I.M.Chiu, and C.Yu (2002).
Oligomerization of acidic fibroblast growth factor is not a prerequisite for its cell proliferation activity.
  Protein Sci, 11, 1050-1061.  
11920675 A.Meddahi, C.Alexakis, D.Papy, J.P.Caruelle, and D.Barritault (2002).
Heparin-like polymer improved healing of gastric and colic ulceration.
  J Biomed Mater Res, 60, 497-501.  
12242295 B.K.Yeh, A.V.Eliseenkova, A.N.Plotnikov, D.Green, J.Pinnell, T.Polat, A.Gritli-Linde, R.J.Linhardt, and M.Mohammadi (2002).
Structural basis for activation of fibroblast growth factor signaling by sucrose octasulfate.
  Mol Cell Biol, 22, 7184-7192.  
12226076 T.Srimathi, T.K.Kumar, Y.H.Chi, I.M.Chiu, and C.Yu (2002).
Characterization of the structure and dynamics of a near-native equilibrium intermediate in the unfolding pathway of an all beta-barrel protein.
  J Biol Chem, 277, 47507-47516.  
10224111 D.A.Pye, and J.T.Gallagher (1999).
Monomer complexes of basic fibroblast growth factor and heparan sulfate oligosaccharides are the minimal functional unit for cell activation.
  J Biol Chem, 274, 13456-13461.  
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.  
10555961 H.Zhou, J.R.Casas-Finet, R.Heath Coats, J.D.Kaufman, S.J.Stahl, P.T.Wingfield, J.S.Rubin, D.P.Bottaro, and R.A.Byrd (1999).
Identification and dynamics of a heparin-binding site in hepatocyte growth factor.
  Biochemistry, 38, 14793-14802.  
10413500 K.M.Patrie, M.J.Botelho, K.Franklin, and I.M.Chiu (1999).
Site-directed mutagenesis and molecular modeling identify a crucial amino acid in specifying the heparin affinity of FGF-1.
  Biochemistry, 38, 9264-9272.  
10400621 S.Vallés, C.Tsoi, W.Y.Huang, D.Wyllie, F.Carlotti, J.A.Askari, M.J.Humphries, S.K.Dower, and E.E.Qwarnström (1999).
Recruitment of a heparan sulfate subunit to the interleukin-1 receptor complex. Regulation by fibronectin attachment.
  J Biol Chem, 274, 20103-20109.  
9665161 G.Waksman, and A.B.Herr (1998).
New insights into heparin-induced FGF oligomerization.
  Nat Struct Biol, 5, 527-530.  
9631661 R.E.Hileman, J.R.Fromm, J.M.Weiler, and R.J.Linhardt (1998).
Glycosaminoglycan-protein interactions: definition of consensus sites in glycosaminoglycan binding proteins.
  Bioessays, 20, 156-167.  
9818261 S.Faham, R.J.Linhardt, and D.C.Rees (1998).
Diversity does make a difference: fibroblast growth factor-heparin interactions.
  Curr Opin Struct Biol, 8, 578-586.  
9106900 D.Blottner (1997).
Nitric oxide and fibroblast growth factor in autonomic nervous system: short- and long-term messengers in autonomic pathway and target-organ control.
  Prog Neurobiol, 51, 423-438.  
9310356 R.M.Lozano, G.Rivas, and G.Giménez-Gallego (1997).
Destabilization, oligomerization and inhibition of the mitogenic activity of acidic fibroblast-growth factor by aurintricarboxylic acid.
  Eur J Biochem, 248, 30-36.  
8729007 E.E.Caldwell, V.D.Nadkarni, J.R.Fromm, R.J.Linhardt, and J.M.Weiler (1996).
Importance of specific amino acids in protein binding sites for heparin and heparan sulfate.
  Int J Biochem Cell Biol, 28, 203-216.  
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.  
7665610 H.Zhu, K.Ramnarayan, J.Anchin, W.Y.Miao, A.Sereno, L.Millman, J.Zheng, V.N.Balaji, and M.E.Wolff (1995).
Glu-96 of basic fibroblast growth factor is essential for high affinity receptor binding. Identification by structure-based site-directed mutagenesis.
  J Biol Chem, 270, 21869-21874.  
8574697 J.M.Rini (1995).
X-ray crystal structures of animal lectins.
  Curr Opin Struct Biol, 5, 617-621.  
8521464 J.Schlessinger, I.Lax, and M.Lemmon (1995).
Regulation of growth factor activation by proteoglycans: what is the role of the low affinity receptors?
  Cell, 83, 357-360.  
8565003 J.Shen, and L.E.Lerner (1995).
A comparison of the conformation of sucrose octasulfate, free and bound to acidic fibroblast growth factor.
  Carbohydr Res, 273, 115-127.  
7592764 P.Wong, B.Hampton, E.Szylobryt, A.M.Gallagher, M.Jaye, and W.H.Burgess (1995).
Analysis of putative heparin-binding domains of fibroblast growth factor-1. Using site-directed mutagenesis and peptide analogues.
  J Biol Chem, 270, 25805-25811.  
  8575190 S.Ernst, R.Langer, C.L.Cooney, and R.Sasisekharan (1995).
Enzymatic degradation of glycosaminoglycans.
  Crit Rev Biochem Mol Biol, 30, 387-444.  
8529231 U.R.Desai, I.R.Vlahov, A.Pervin, and R.J.Linhardt (1995).
Conformational analysis of sucrose octasulfate by high resolution nuclear magnetic resonance spectroscopy.
  Carbohydr Res, 275, 391-401.  
7528103 T.Spivak-Kroizman, M.A.Lemmon, I.Dikic, J.E.Ladbury, D.Pinchasi, J.Huang, M.Jaye, G.Crumley, J.Schlessinger, and I.Lax (1994).
Heparin-induced oligomerization of FGF molecules is responsible for FGF receptor dimerization, activation, and cell proliferation.
  Cell, 79, 1015-1024.  
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 code is shown on the right.

 

spacer
spacer