PDBsum entry 1bfc

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protein ligands links
Growth factor PDB id
Protein chain
124 a.a. *
Waters ×14
* Residue conservation analysis
PDB id:
Name: Growth factor
Title: Basic fibroblast growth factor complexed with heparin hexame
Structure: Basic fibroblast growth factor. Chain: a. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
2.20Å     R-factor:   0.188    
Authors: S.Faham,D.C.Rees
Key ref: S.Faham et al. (1996). Heparin structure and interactions with basic fibroblast growth factor. Science, 271, 1116-1120. PubMed id: 8599088 DOI: 10.1126/science.271.5252.1116
12-Dec-95     Release date:   03-Apr-96    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P09038  (FGF2_HUMAN) -  Fibroblast growth factor 2
288 a.a.
124 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     fibroblast growth factor receptor signaling pathway   1 term 
  Biochemical function     receptor binding     3 terms  


DOI no: 10.1126/science.271.5252.1116 Science 271:1116-1120 (1996)
PubMed id: 8599088  
Heparin structure and interactions with basic fibroblast growth factor.
S.Faham, R.E.Hileman, J.R.Fromm, R.J.Linhardt, D.C.Rees.
Crystal structures of heparin-derived tetra- and hexasaccharides complexed with basic fibroblast growth factor (bFGF) were determined at resolutions of 1.9 and 2.2 angstroms, respectively. The heparin structure may be approximated as a helical polymer with a disaccharide rotation of 174 degrees and a translation of 8.6 angstroms along the helix axis. Both molecules bound similarly to a region of the bFGF surface containing residues asparagine-28, arginine-121, lysine-126, and glutamine-135, the hexasaccharide also interacted with an additional binding site formed by lysine-27, asparagine-102, and lysine-136. No significant conformational change in bFGF occurred upon heparin oligosaccharide binding, which suggests that heparin primarily serves to juxtapose components of the FGF signal transduction pathway.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21142700 J.E.Tengood, R.Ridenour, R.Brodsky, A.J.Russell, and S.R.Little (2011).
Sequential delivery of basic fibroblast growth factor and platelet-derived growth factor for angiogenesis.
  Tissue Eng Part A, 17, 1181-1189.  
20213669 M.Torrent, M.V.Nogués, and E.Boix (2011).
Eosinophil cationic protein (ECP) can bind heparin and other glycosaminoglycans through its RNase active site.
  J Mol Recognit, 24, 90.  
20379137 A.K.Powell, Y.A.Ahmed, E.A.Yates, and J.E.Turnbull (2010).
Generating heparan sulfate saccharide libraries for glycomics applications.
  Nat Protoc, 5, 821-833.  
20674970 A.Zieris, S.Prokoph, K.R.Levental, P.B.Welzel, M.Grimmer, U.Freudenberg, and C.Werner (2010).
FGF-2 and VEGF functionalization of starPEG-heparin hydrogels to modulate biomolecular and physical cues of angiogenesis.
  Biomaterials, 31, 7985-7994.  
19851836 A.Zieris, S.Prokoph, P.B.Welzel, M.Grimmer, K.R.Levental, W.Panyanuwat, U.Freudenberg, and C.Werner (2010).
Analytical approaches to uptake and release of hydrogel-associated FGF-2.
  J Mater Sci Mater Med, 21, 915-923.  
20543985 B.J.Zern, H.Chu, and Y.Wang (2010).
Control growth factor release using a self-assembled [polycation:heparin] complex.
  PLoS One, 5, e11017.  
20657775 C.L.Cole, S.U.Hansen, M.Baráth, G.Rushton, J.M.Gardiner, E.Avizienyte, and G.C.Jayson (2010).
Synthetic heparan sulfate oligosaccharides inhibit endothelial cell functions essential for angiogenesis.
  PLoS One, 5, e11644.  
19906646 J.T.Hoopes, X.Liu, X.Xu, B.Demeler, E.Folta-Stogniew, C.Li, and Y.Ha (2010).
Structural characterization of the E2 domain of APL-1, a Caenorhabditis elegans homolog of human amyloid precursor protein, and its heparin binding site.
  J Biol Chem, 285, 2165-2173.
PDB codes: 3k66 3k6b
20155753 T.Crouzier, A.Szarpak, T.Boudou, R.Auzély-Velty, and C.Picart (2010).
Polysaccharide-blend multilayers containing hyaluronan and heparin as a delivery system for rhBMP-2.
  Small, 6, 651-662.  
20621352 Y.J.Choi, J.Y.Lee, J.H.Park, J.B.Park, J.S.Suh, Y.S.Choi, S.J.Lee, C.P.Chung, and Y.J.Park (2010).
The identification of a heparin binding domain peptide from bone morphogenetic protein-4 and its role on osteogenesis.
  Biomaterials, 31, 7226-7238.  
20623566 Z.Wang, Y.Xu, B.Yang, G.Tiruchinapally, B.Sun, R.Liu, S.Dulaney, J.Liu, and X.Huang (2010).
Preactivation-based, one-pot combinatorial synthesis of heparin-like hexasaccharides for the analysis of heparin-protein interactions.
  Chemistry, 16, 8365-8375.  
19567366 A.Ori, P.Free, J.Courty, M.C.Wilkinson, and D.G.Fernig (2009).
Identification of heparin-binding sites in proteins by selective labeling.
  Mol Cell Proteomics, 8, 2256-2265.  
19800090 C.J.Lehiy, O.Martinez, and A.L.Passarelli (2009).
Virion-associated viral fibroblast growth factor stimulates cell motility.
  Virology, 395, 152-160.  
19144372 J.O'Donnell, K.A.Taylor, and M.S.Chapman (2009).
Adeno-associated virus-2 and its primary cellular receptor--Cryo-EM structure of a heparin complex.
  Virology, 385, 434-443.  
19648354 L.Jin, M.Hricovíni, J.A.Deakin, M.Lyon, and D.Uhrín (2009).
Residual dipolar coupling investigation of a heparin tetrasaccharide confirms the limited effect of flexibility of the iduronic acid on the molecular shape of heparin.
  Glycobiology, 19, 1185-1196.  
19187003 M.Boodhwani, and F.W.Sellke (2009).
Therapeutic angiogenesis in diabetes and hypercholesterolemia: influence of oxidative stress.
  Antioxid Redox Signal, 11, 1945-1959.  
19925012 M.R.Schenauer, J.K.Meissen, Y.Seo, J.B.Ames, and J.A.Leary (2009).
Heparan sulfate separation, sequencing, and isomeric differentiation: ion mobility spectrometry reveals specific iduronic and glucuronic acid-containing hexasaccharides.
  Anal Chem, 81, 10179-10185.  
19751661 O.Lieleg, R.M.Baumgärtel, and A.R.Bausch (2009).
Selective filtering of particles by the extracellular matrix: an electrostatic bandpass.
  Biophys J, 97, 1569-1577.  
18178534 R.O.Craft, J.Rophael, W.A.Morrison, A.V.Vashi, G.M.Mitchell, and A.J.Penington (2009).
Effect of local, long-term delivery of platelet-derived growth factor (PDGF) on injected fat graft survival in severe combined immunodeficient (SCID) mice.
  J Plast Reconstr Aesthet Surg, 62, 235-243.  
19254961 S.Ashikari-Hada, H.Habuchi, N.Sugaya, T.Kobayashi, and K.Kimata (2009).
Specific inhibition of FGF-2 signaling with 2-O-sulfated octasaccharides of heparan sulfate.
  Glycobiology, 19, 644-654.  
18589009 A.J.Brown, M.Alicknavitch, S.S.D'Souza, T.Daikoku, C.B.Kirn-Safran, D.Marchetti, D.D.Carson, and M.C.Farach-Carson (2008).
Heparanase expression and activity influences chondrogenic and osteogenic processes during endochondral bone formation.
  Bone, 43, 689-699.  
18288776 A.Liang, X.Liu, Y.Du, K.Wang, and B.Lin (2008).
Further characterization of the binding of heparin to granulocyte colony-stimulating factor: importance of sulfate groups.
  Electrophoresis, 29, 1286-1290.  
18800386 D.G.Seidler, and R.Dreier (2008).
Decorin and its galactosaminoglycan chain: extracellular regulator of cellular function?
  IUBMB Life, 60, 729-733.  
18698580 D.H.Go, Y.K.Joung, S.Y.Lee, M.C.Lee, and K.D.Park (2008).
Tetronic-oligolactide-heparin hydrogel as a multi-functional scaffold for tissue regeneration.
  Macromol Biosci, 8, 1152-1160.  
18041729 D.H.Go, Y.K.Joung, S.Y.Park, Y.D.Park, and K.D.Park (2008).
Heparin-conjugated star-shaped PLA for improved biocompatibility.
  J Biomed Mater Res A, 86, 842-848.  
18493641 E.Gemma, O.Meyer, D.Uhrín, and A.N.Hulme (2008).
Enabling methodology for the end functionalization of glycosaminoglycan oligosaccharides.
  Mol Biosyst, 4, 481-495.  
18163458 M.Fannon, K.Forsten-Williams, M.A.Nugent, K.J.Gregory, C.L.Chu, A.L.Goerges-Wildt, D.Panigrahy, A.Kaipainen, C.Barnes, C.Lapp, and Y.Shing (2008).
Sucrose octasulfate regulates fibroblast growth factor-2 binding, transport, and activity: potential for regulation of tumor growth.
  J Cell Physiol, 215, 434-441.  
19090915 N.S.Gandhi, and R.L.Mancera (2008).
The structure of glycosaminoglycans and their interactions with proteins.
  Chem Biol Drug Des, 72, 455-482.  
18541909 R.G.Thorne, A.Lakkaraju, E.Rodriguez-Boulan, and C.Nicholson (2008).
In vivo diffusion of lactoferrin in brain extracellular space is regulated by interactions with heparan sulfate.
  Proc Natl Acad Sci U S A, 105, 8416-8421.  
17593974 C.R.Holst, H.Bou-Reslan, B.B.Gore, K.Wong, D.Grant, S.Chalasani, R.A.Carano, G.D.Frantz, M.Tessier-Lavigne, B.Bolon, D.M.French, and A.Ashkenazi (2007).
Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival.
  PLoS ONE, 2, e575.  
17478502 C.X.Weichenberger, and M.J.Sippl (2007).
NQ-Flipper: recognition and correction of erroneous asparagine and glutamine side-chain rotamers in protein structures.
  Nucleic Acids Res, 35, W403-W406.  
17594020 E.Gemma, A.N.Hulme, A.Jahnke, L.Jin, M.Lyon, R.M.Müller, and D.Uhrín (2007).
DMT-MM mediated functionalisation of the non-reducing end of glycosaminoglycans.
  Chem Commun (Camb), (), 2686-2688.  
17317573 E.L.Shipp, and L.C.Hsieh-Wilson (2007).
Profiling the sulfation specificities of glycosaminoglycan interactions with growth factors and chemotactic proteins using microarrays.
  Chem Biol, 14, 195-208.  
17393303 I.Kashiwakura, K.Takahashi, and K.Takagaki (2007).
Application of proteoglycan extracted from the nasal cartilage of salmon heads for ex vivo expansion of hematopoietic progenitor cells derived from human umbilical cord blood.
  Glycoconj J, 24, 251-258.  
17509717 J.Guan, J.J.Stankus, and W.R.Wagner (2007).
Biodegradable elastomeric scaffolds with basic fibroblast growth factor release.
  J Control Release, 120, 70-78.  
17719487 Paz, C.Noti, F.Böhm, S.Werner, and P.H.Seeberger (2007).
Potentiation of fibroblast growth factor activity by synthetic heparin oligosaccharide glycodendrimers.
  Chem Biol, 14, 879-887.  
17580326 J.Y.Lee, J.E.Choo, Y.S.Choi, K.Y.Lee, D.S.Min, S.H.Pi, Y.J.Seol, S.J.Lee, I.H.Jo, C.P.Chung, and Y.J.Park (2007).
Characterization of the surface immobilized synthetic heparin binding domain derived from human fibroblast growth factor-2 and its effect on osteoblast differentiation.
  J Biomed Mater Res A, 83, 970-979.  
17719484 R.Raman, and R.Sasisekharan (2007).
Cooperativity in glycan-protein interactions.
  Chem Biol, 14, 873-874.  
17305366 S.C.Hrtska, M.M.Kemp, E.M.Muñoz, O.Azizad, M.Banerjee, C.Raposo, J.Kumaran, P.Ghosh, and R.J.Linhardt (2007).
Investigation of the mechanism of binding between internalin B and heparin using surface plasmon resonance.
  Biochemistry, 46, 2697-2706.  
16995857 A.Canales, R.Lozano, B.López-Méndez, J.Angulo, R.Ojeda, P.M.Nieto, M.Martín-Lomas, G.Giménez-Gallego, and J.Jiménez-Barbero (2006).
Solution NMR structure of a human FGF-1 monomer, activated by a hexasaccharide heparin-analogue.
  FEBS J, 273, 4716-4727.
PDB code: 2erm
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.  
16759098 A.Raghuraman, P.D.Mosier, and U.R.Desai (2006).
Finding a needle in a haystack: development of a combinatorial virtual screening approach for identifying high specificity heparin/heparan sulfate sequence(s).
  J Med Chem, 49, 3553-3562.  
16822883 A.Schmidt, D.Ladage, T.Schinköthe, U.Klausmann, C.Ulrichs, F.J.Klinz, K.Brixius, S.Arnhold, B.Desai, U.Mehlhorn, R.H.Schwinger, P.Staib, K.Addicks, and W.Bloch (2006).
Basic fibroblast growth factor controls migration in human mesenchymal stem cells.
  Stem Cells, 24, 1750-1758.  
17518619 A.V.Vashi, K.M.Abberton, G.P.Thomas, W.A.Morrison, A.J.O'Connor, J.J.Cooper-White, and E.W.Thompson (2006).
Adipose tissue engineering based on the controlled release of fibroblast growth factor-2 in a collagen matrix.
  Tissue Eng, 12, 3035-3043.  
16539678 B.Hui, W.Xia, J.Li, L.Wang, J.Ai, and M.Geng (2006).
Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome drug candidate, blocks neuroinflammatory signalling by targeting the transactivator of transcription (Tat) protein.
  J Neurochem, 97, 334-344.  
16740958 C.L.Lawson, B.H.Yung, A.G.Barbour, and W.R.Zückert (2006).
Crystal structure of neurotropism-associated variable surface protein 1 (Vsp1) of Borrelia turicatae.
  J Bacteriol, 188, 4522-4530.
PDB codes: 1yjg 2ga0
16765889 C.X.Weichenberger, and M.J.Sippl (2006).
Self-consistent assignment of asparagine and glutamine amide rotamers in protein crystal structures.
  Structure, 14, 967-972.  
17030799 C.Zehe, A.Engling, S.Wegehingel, T.Schäfer, and W.Nickel (2006).
Cell-surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2.
  Proc Natl Acad Sci U S A, 103, 15479-15484.  
16890321 L.Zhang, E.M.Furst, and K.L.Kiick (2006).
Manipulation of hydrogel assembly and growth factor delivery via the use of peptide-polysaccharide interactions.
  J Control Release, 114, 130-142.  
16222707 M.Bodo, T.Baroni, C.Bellucci, C.Lilli, M.De Ioanni, E.Bonifacio, L.Moretti, E.Becchetti, S.Bellocchio, C.Delfini, E.Lumare, and A.Tabilio (2006).
Unique human CD133+ leukemia cell line and its modulation towards a mesenchymal phenotype by FGF2 and TGFbeta1.
  J Cell Physiol, 206, 682-692.  
16980878 M.Boodhwani, N.R.Sodha, R.J.Laham, and F.W.Sellke (2006).
The future of therapeutic myocardial angiogenesis.
  Shock, 26, 332-341.  
16933356 M.W.Schelle, and C.R.Bertozzi (2006).
Sulfate metabolism in mycobacteria.
  Chembiochem, 7, 1516-1524.  
16835755 R.R.Gomes, T.H.Van Kuppevelt, M.C.Farach-Carson, and D.D.Carson (2006).
Spatiotemporal distribution of heparan sulfate epitopes during murine cartilage growth plate development.
  Histochem Cell Biol, 126, 713-722.  
16834555 R.Sasisekharan, R.Raman, and V.Prabhakar (2006).
Glycomics approach to structure-function relationships of glycosaminoglycans.
  Annu Rev Biomed Eng, 8, 181-231.  
16100743 A.Liang, Y.Chao, X.Liu, Y.Du, K.Wang, S.Qian, and B.Lin (2005).
Separation, identification, and interaction of heparin oligosaccharides with granulocyte-colony stimulating factor using capillary electrophoresis and mass spectrometry.
  Electrophoresis, 26, 3460-3467.  
16233851 H.Mori, Y.Kanemura, J.Onaya, M.Hara, J.Miyake, M.Yamasaki, and Y.Kariya (2005).
Effects of heparin and its 6-O-and 2-O-desulfated derivatives with low anticoagulant activity on proliferation of human neural stem/progenitor cells.
  J Biosci Bioeng, 100, 54-61.  
16273147 L.Jin, P.E.Barran, J.A.Deakin, M.Lyon, and D.Uhrín (2005).
Conformation of glycosaminoglycans by ion mobility mass spectrometry and molecular modelling.
  Phys Chem Chem Phys, 7, 3464-3471.  
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.  
16154740 M.Mohammadi, S.K.Olsen, and R.Goetz (2005).
A protein canyon in the FGF-FGF receptor dimer selects from an à la carte menu of heparan sulfate motifs.
  Curr Opin Struct Biol, 15, 506-516.  
16004429 N.Yamaguchi, and K.L.Kiick (2005).
Polysaccharide-poly(ethylene glycol) star copolymer as a scaffold for the production of bioactive hydrogels.
  Biomacromolecules, 6, 1921-1930.  
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.  
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.  
15952892 T.M.Handel, Z.Johnson, S.E.Crown, E.K.Lau, and A.E.Proudfoot (2005).
Regulation of protein function by glycosaminoglycans--as exemplified by chemokines.
  Annu Rev Biochem, 74, 385-410.  
15973728 T.Nagayasu, S.Miyata, N.Hayashi, R.Takano, Y.Kariya, and K.Kamei (2005).
Heparin structures in FGF-2-dependent morphological transformation of astrocytes.
  J Biomed Mater Res A, 74, 374-380.  
16072037 U.Häcker, K.Nybakken, and N.Perrimon (2005).
Heparan sulphate proteoglycans: the sweet side of development.
  Nat Rev Mol Cell Biol, 6, 530-541.  
15688452 W.Tempel, Z.J.Liu, P.S.Horanyi, L.Deng, D.Lee, M.G.Newton, J.P.Rose, H.Ashida, S.C.Li, Y.T.Li, and B.C.Wang (2005).
Three-dimensional structure of GlcNAcalpha1-4Gal releasing endo-beta-galactosidase from Clostridium perfringens.
  Proteins, 59, 141-144.
PDB code: 1ups
15990353 Z.Johnson, A.E.Proudfoot, and T.M.Handel (2005).
Interaction of chemokines and glycosaminoglycans: a new twist in the regulation of chemokine function with opportunities for therapeutic intervention.
  Cytokine Growth Factor Rev, 16, 625-636.  
15151475 A.Rosinberg, T.A.Khan, F.W.Sellke, and R.J.Laham (2004).
Therapeutic angiogenesis for myocardial ischemia.
  Expert Rev Cardiovasc Ther, 2, 271-283.  
14997572 E.Krieger, E.Geretti, B.Brandner, B.Goger, T.N.Wells, and A.J.Kungl (2004).
A structural and dynamic model for the interaction of interleukin-8 and glycosaminoglycans: support from isothermal fluorescence titrations.
  Proteins, 54, 768-775.  
15206937 G.A.Nicolaes, K.W.Sørensen, U.Friedrich, G.Tans, J.Rosing, L.Autin, B.Dahlbäck, and B.O.Villoutreix (2004).
Altered inactivation pathway of factor Va by activated protein C in the presence of heparin.
  Eur J Biochem, 271, 2724-2736.  
14695513 J.Angulo, R.Ojeda, Paz, R.Lucas, P.M.Nieto, R.M.Lozano, M.Redondo-Horcajo, G.Giménez-Gallego, and M.Martín-Lomas (2004).
The activation of fibroblast growth factors (FGFs) by glycosaminoglycans: influence of the sulfation pattern on the biological activity of FGF-1.
  Chembiochem, 5, 55-61.  
14699503 J.P.Lai, J.R.Chien, D.R.Moser, J.K.Staub, I.Aderca, D.P.Montoya, T.A.Matthews, D.M.Nagorney, J.M.Cunningham, D.I.Smith, E.L.Greene, V.Shridhar, and L.R.Roberts (2004).
hSulf1 Sulfatase promotes apoptosis of hepatocellular cancer cells by decreasing heparin-binding growth factor signaling.
  Gastroenterology, 126, 231-248.  
15334632 T.Sato, A.Yamaguchi, T.Goi, Y.Hirono, K.Takeuchi, K.Katayama, and S.Matsukawa (2004).
Heparanase expression in human colorectal cancer and its relationship to tumor angiogenesis, hematogenous metastasis, and prognosis.
  J Surg Oncol, 87, 174-181.  
15178763 V.K.Ganesh, S.A.Smith, G.J.Kotwal, and K.H.Murthy (2004).
Structure of vaccinia complement protein in complex with heparin and potential implications for complement regulation.
  Proc Natl Acad Sci U S A, 101, 8924-8929.
PDB code: 1rid
14610064 B.L.Allen, and A.C.Rapraeger (2003).
Spatial and temporal expression of heparan sulfate in mouse development regulates FGF and FGF receptor assembly.
  J Cell Biol, 163, 637-648.  
12939521 L.Wang, M.Geng, J.Li, H.Guan, and J.Ding (2003).
Studies of marine sulfated polymannuroguluronate on endothelial cell proliferation and endothelial immunity and related mechanisms.
  J Pharmacol Sci, 92, 367-373.  
14507732 P.E.Marszalek, A.F.Oberhauser, H.Li, and J.M.Fernandez (2003).
The force-driven conformations of heparin studied with single molecule force microscopy.
  Biophys J, 85, 2696-2704.  
12604799 R.Raman, G.Venkataraman, S.Ernst, V.Sasisekharan, and R.Sasisekharan (2003).
Structural specificity of heparin binding in the fibroblast growth factor family of proteins.
  Proc Natl Acad Sci U S A, 100, 2357-2362.  
12583005 V.Dimitrellos, F.N.Lamari, M.Militsopoulou, I.Kanakis, and N.K.Karamanos (2003).
Capillary electrophoresis and enzyme solid phase assay for examining the purity of a synthetic heparin proteoglycan-like conjugate and identifying binding to basic fibroblast growth factor.
  Biomed Chromatogr, 17, 42-47.  
12461785 W.Li, M.A.Nugent, Y.Zhao, A.N.Chau, S.J.Li, I.N.Chou, G.Liu, and H.M.Kagan (2003).
Lysyl oxidase oxidizes basic fibroblast growth factor and inactivates its mitogenic potential.
  J Cell Biochem, 88, 152-164.  
14502551 Y.Luo, H.H.Cho, and W.L.McKeehan (2003).
Biospecific extraction and neutralization of anticoagulant heparin with fibroblast growth factors (FGF).
  J Pharm Sci, 92, 2117-2127.  
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.  
12359625 A.K.Ghosh, N.Hirasawa, Y.S.Lee, Y.S.Kim, K.H.Shin, N.Ryu, and K.Ohuchi (2002).
Inhibition by acharan sulphate of angiogenesis in experimental inflammation models.
  Br J Pharmacol, 137, 441-448.  
11805308 A.Varki (2002).
Six blind men and the elephant--the many faces of heparan sulfate.
  Proc Natl Acad Sci U S A, 99, 543-545.  
12395423 E.K.Davies, M.Glick, K.N.Harrison, and W.G.Richards (2002).
Pattern recognition and massively distributed computing.
  J Comput Chem, 23, 1544-1550.  
11857642 F.N.Lamari, M.Militsopoulou, T.N.Mitropoulou, A.Hjerpe, and N.K.Karamanos (2002).
Analysis of glycosaminoglycan-derived disaccharides in biologic samples by capillary electrophoresis and protocol for sequencing glycosaminoglycans.
  Biomed Chromatogr, 16, 95.  
12491369 I.Capila, and R.J.Linhardt (2002).
Heparin-protein interactions.
  Angew Chem Int Ed Engl, 41, 391-412.  
12456637 J.Kreuger, T.Matsumoto, M.Vanwildemeersch, T.Sasaki, R.Timpl, L.Claesson-Welsh, D.Spillmann, and U.Lindahl (2002).
Role of heparan sulfate domain organization in endostatin inhibition of endothelial cell function.
  EMBO J, 21, 6303-6311.  
11746174 J.Liu, and S.C.Thorp (2002).
Cell surface heparan sulfate and its roles in assisting viral infections.
  Med Res Rev, 22, 1.  
12369092 K.Honke, and N.Taniguchi (2002).
Sulfotransferases and sulfated oligosaccharides.
  Med Res Rev, 22, 637-654.  
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.  
11863456 P.Stenlund, M.J.Lindberg, and L.A.Tibell (2002).
Structural requirements for high-affinity heparin binding: alanine scanning analysis of charged residues in the C-terminal domain of human extracellular superoxide dismutase.
  Biochemistry, 41, 3168-3175.  
11792229 T.A.Khan, F.W.Sellke, and R.J.Laham (2002).
Therapeutic Angiogenesis for Coronary Artery Disease.
  Curr Treat Options Cardiovasc Med, 4, 65-74.  
11785765 B.Mulloy, and R.J.Linhardt (2001).
Order out of complexity--protein structures that interact with heparin.
  Curr Opin Struct Biol, 11, 623-628.  
11597998 D.Lietha, D.Y.Chirgadze, B.Mulloy, T.L.Blundell, and E.Gherardi (2001).
Crystal structures of NK1-heparin complexes reveal the basis for NK1 activity and enable engineering of potent agonists of the MET receptor.
  EMBO J, 20, 5543-5555.
PDB codes: 1gmn 1gmo
11223514 H.J.Hecht, R.Adar, B.Hofmann, O.Bogin, H.Weich, and A.Yayon (2001).
Structure of fibroblast growth factor 9 shows a symmetric dimer with unique receptor- and heparin-binding interfaces.
  Acta Crystallogr D Biol Crystallogr, 57, 378-384.
PDB code: 1g82
11342135 I.Capila, M.J.Hernáiz, Y.D.Mo, T.R.Mealy, B.Campos, J.R.Dedman, R.J.Linhardt, and B.A.Seaton (2001).
Annexin V--heparin oligosaccharide complex suggests heparan sulfate--mediated assembly on cell surfaces.
  Structure, 9, 57-64.
PDB code: 1g5n
11331020 J.Rong, H.Habuchi, K.Kimata, U.Lindahl, and M.Kusche-Gullberg (2001).
Substrate specificity of the heparan sulfate hexuronic acid 2-O-sulfotransferase.
  Biochemistry, 40, 5548-5555.  
  11489926 J.T.Gallagher (2001).
Heparan sulfate: growth control with a restricted sequence menu.
  J Clin Invest, 108, 357-361.  
11207370 K.H.Murthy, S.A.Smith, V.K.Ganesh, K.W.Judge, N.Mullin, P.N.Barlow, C.M.Ogata, and G.J.Kotwal (2001).
Crystal structure of a complement control protein that regulates both pathways of complement activation and binds heparan sulfate proteoglycans.
  Cell, 104, 301-311.
PDB codes: 1g40 1g44
11371192 L.Martin, C.Blanpain, P.Garnier, V.Wittamer, M.Parmentier, and C.Vita (2001).
Structural and functional analysis of the RANTES-glycosaminoglycans interactions.
  Biochemistry, 40, 6303-6318.  
11785766 L.Pellegrini (2001).
Role of heparan sulfate in fibroblast growth factor signalling: a structural view.
  Curr Opin Struct Biol, 11, 629-634.  
11165170 S.Hemmerich (2001).
Carbohydrate sulfotransferases: novel therapeutic targets for inflammation, viral infection and cancer.
  Drug Discov Today, 6, 27-35.  
11724555 S.Ye, Y.Luo, W.Lu, R.B.Jones, R.J.Linhardt, I.Capila, T.Toida, M.Kan, H.Pelletier, and W.L.McKeehan (2001).
Structural basis for interaction of FGF-1, FGF-2, and FGF-7 with different heparan sulfate motifs.
  Biochemistry, 40, 14429-14439.
PDB codes: 1qqk 1qql
11579452 T.Miura, and T.Kajimoto (2001).
Application of L-threonine aldolase-catalyzed reaction to the preparation of protected 3R,5R-dihydroxy-L-homoproline as a mimetic of idulonic acid.
  Chirality, 13, 577-580.  
10625498 A.Lookene, P.Stenlund, and L.A.Tibell (2000).
Characterization of heparin binding of human extracellular superoxide dismutase.
  Biochemistry, 39, 230-236.  
10618369 D.J.Stauber, A.D.DiGabriele, and W.A.Hendrickson (2000).
Structural interactions of fibroblast growth factor receptor with its ligands.
  Proc Natl Acad Sci U S A, 97, 49-54.
PDB code: 1djs
10978168 F.Safaiyan, U.Lindahl, and M.Salmivirta (2000).
Structural diversity of N-sulfated heparan sulfate domains: distinct modes of glucuronyl C5 epimerization, iduronic acid 2-O-sulfation, and glucosamine 6-O-sulfation.
  Biochemistry, 39, 10823-10830.  
  11270504 H.Shibata, I.Kimura-Takagi, M.Nagaoka, S.Hashimoto, R.Aiyama, M.Iha, S.Ueyama, and T.Yokokura (2000).
Properties of fucoidan from Cladosiphon okamuranus tokida in gastric mucosal protection.
  Biofactors, 11, 235-245.  
11030354 J.Schlessinger, A.N.Plotnikov, O.A.Ibrahimi, A.V.Eliseenkova, B.K.Yeh, A.Yayon, R.J.Linhardt, and M.Mohammadi (2000).
Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization.
  Mol Cell, 6, 743-750.
PDB code: 1fq9
10687947 M.A.Nugent, and R.V.Iozzo (2000).
Fibroblast growth factor-2.
  Int J Biochem Cell Biol, 32, 115-120.  
11271497 M.J.Hubbard, and N.J.McHugh (2000).
Human ERp29: isolation, primary structural characterisation and two-dimensional gel mapping.
  Electrophoresis, 21, 3785-3796.  
11127452 R.J.Laham, N.A.Chronos, M.Pike, M.E.Leimbach, J.E.Udelson, J.D.Pearlman, R.I.Pettigrew, M.J.Whitehouse, C.Yoshizawa, and M.Simons (2000).
Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a phase I open-label dose escalation study.
  J Am Coll Cardiol, 36, 2132-2139.  
10736176 S.P.Hari, H.McAllister, W.L.Chuang, M.D.Christ, and D.L.Rabenstein (2000).
Interaction of heparin with a synthetic pentadecapeptide from the C-terminal heparin-binding domain of fibronectin.
  Biochemistry, 39, 3763-3773.  
10716625 S.Tumova, A.Woods, and J.R.Couchman (2000).
Heparan sulfate proteoglycans on the cell surface: versatile coordinators of cellular functions.
  Int J Biochem Cell Biol, 32, 269-288.  
11076027 T.L.Blundell, D.F.Burke, D.Chirgadze, V.Dhanaraj, M.Hyvönen, C.A.Innis, E.Parisini, L.Pellegrini, M.Sayed, and B.L.Sibanda (2000).
Protein-protein interactions in receptor activation and intracellular signalling.
  Biol Chem, 381, 955-959.  
10736153 W.L.Chuang, M.D.Christ, J.Peng, and D.L.Rabenstein (2000).
An NMR and molecular modeling study of the site-specific binding of histamine by heparin, chemically modified heparin, and heparin-derived oligosaccharides.
  Biochemistry, 39, 3542-3555.  
10490103 A.N.Plotnikov, J.Schlessinger, S.R.Hubbard, and M.Mohammadi (1999).
Structural basis for FGF receptor dimerization and activation.
  Cell, 98, 641-650.
PDB code: 1cvs
10075919 A.Sharma, J.A.Askari, M.J.Humphries, E.Y.Jones, and D.I.Stuart (1999).
Crystal structure of a heparin- and integrin-binding segment of human fibronectin.
  EMBO J, 18, 1468-1479.
PDB code: 1fnh
  10531225 B.K.Choi, and D.M.Schifferli (1999).
Lysine residue 117 of the FasG adhesin of enterotoxigenic Escherichia coli is essential for binding of 987P fimbriae to sulfatide.
  Infect Immun, 67, 5755-5761.  
9927414 E.E.Fry, S.M.Lea, T.Jackson, J.W.Newman, F.M.Ellard, W.E.Blakemore, R.Abu-Ghazaleh, A.Samuel, A.M.King, and D.I.Stuart (1999).
The structure and function of a foot-and-mouth disease virus-oligosaccharide receptor complex.
  EMBO J, 18, 543-554.
PDB codes: 1fhp 1qqp
10398402 F.Lustig, J.Hoebeke, C.Simonson, G.Ostergren-Lundén, G.Bondjers, U.Rüetchi, and G.Fager (1999).
Processing of PDGF gene products determines interactions with glycosaminoglycans.
  J Mol Recognit, 12, 112-120.  
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.  
9889154 K.G.Bowman, and C.R.Bertozzi (1999).
Carbohydrate sulfotransferases: mediators of extracellular communication.
  Chem Biol, 6, R9.  
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.  
10872465 M.Bernfield, M.Götte, P.W.Park, O.Reizes, M.L.Fitzgerald, J.Lincecum, and M.Zako (1999).
Functions of cell surface heparan sulfate proteoglycans.
  Annu Rev Biochem, 68, 729-777.  
  10631998 M.C.Golden, K.A.Resing, B.D.Collins, M.C.Willis, and T.H.Koch (1999).
Mass spectral characterization of a protein-nucleic acid photocrosslink.
  Protein Sci, 8, 2806-2812.  
10215897 M.Hricovíni, M.Guerrini, and A.Bisio (1999).
Structure of heparin-derived tetrasaccharide complexed to the plasma protein antithrombin derived from NOEs, J-couplings and chemical shifts.
  Eur J Biochem, 261, 789-801.  
10404599 M.T.Huhtala, O.T.Pentikäinen, and M.S.Johnson (1999).
A dimeric ternary complex of FGFR [correction of FGFR1], heparin and FGF-1 leads to an 'electrostatic sandwich' model for heparin binding.
  Structure, 7, 699-709.
PDB code: 1qct
10504408 N.Hosoda, S.I.Hoshino, Y.Kanda, and T.Katada (1999).
Inhibition of phosphodiesterase/pyrophosphatase activity of PC-1 by its association with glycosaminoglycans.
  Eur J Biochem, 265, 763-770.  
10574766 S.E.Guimond, and J.E.Turnbull (1999).
Fibroblast growth factor receptor signalling is dictated by specific heparan sulphate saccharides.
  Curr Biol, 9, 1343-1346.  
10562536 T.Sasaki, H.Larsson, J.Kreuger, M.Salmivirta, L.Claesson-Welsh, U.Lindahl, E.Hohenester, and R.Timpl (1999).
Structural basis and potential role of heparin/heparan sulfate binding to the angiogenesis inhibitor endostatin.
  EMBO J, 18, 6240-6248.  
10029547 Y.R.Hsu, R.Nybo, J.K.Sullivan, V.Costigan, C.S.Spahr, C.Wong, M.Jones, A.G.Pentzer, J.A.Crouse, R.E.Pacifici, H.S.Lu, C.F.Morris, and J.S.Philo (1999).
Heparin is essential for a single keratinocyte growth factor molecule to bind and form a complex with two molecules of the extracellular domain of its receptor.
  Biochemistry, 38, 2523-2534.  
9501087 E.Hohenester, T.Sasaki, B.R.Olsen, and R.Timpl (1998).
Crystal structure of the angiogenesis inhibitor endostatin at 1.5 A resolution.
  EMBO J, 17, 1656-1664.
PDB code: 1koe
9698365 G.S.Kuschert, A.J.Hoogewerf, A.E.Proudfoot, C.W.Chung, R.M.Cooke, R.E.Hubbard, T.N.Wells, and P.N.Sanderson (1998).
Identification of a glycosaminoglycan binding surface on human interleukin-8.
  Biochemistry, 37, 11193-11201.  
9665161 G.Waksman, and A.B.Herr (1998).
New insights into heparin-induced FGF oligomerization.
  Nat Struct Biol, 5, 527-530.  
9493272 H.Zhou, M.J.Mazzulla, J.D.Kaufman, S.J.Stahl, P.T.Wingfield, J.S.Rubin, D.P.Bottaro, and R.A.Byrd (1998).
The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site.
  Structure, 6, 109-116.
PDB code: 2hgf
9751161 J.M.Greene, Y.L.Li, P.A.Yourey, J.Gruber, K.C.Carter, B.K.Shell, P.A.Dillon, C.Florence, D.R.Duan, A.Blunt, D.M.Ornitz, S.M.Ruben, and R.F.Alderson (1998).
Identification and characterization of a novel member of the fibroblast growth factor family.
  Eur J Neurosci, 10, 1911-1925.  
9623978 M.Kato, H.Wang, V.Kainulainen, M.L.Fitzgerald, S.Ledbetter, D.M.Ornitz, and M.Bernfield (1998).
Physiological degradation converts the soluble syndecan-1 ectodomain from an inhibitor to a potent activator of FGF-2.
  Nat Med, 4, 691-697.  
9817840 M.Ultsch, N.A.Lokker, P.J.Godowski, and Vos (1998).
Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 A resolution.
  Structure, 6, 1383-1393.
PDB code: 1bht
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.  
9461194 M.Zhou, R.L.Sutliff, R.J.Paul, J.N.Lorenz, J.B.Hoying, C.C.Haudenschild, M.Yin, J.D.Coffin, L.Kong, E.G.Kranias, W.Luo, G.P.Boivin, J.J.Duffy, S.A.Pawlowski, and T.Doetschman (1998).
Fibroblast growth factor 2 control of vascular tone.
  Nat Med, 4, 201-207.  
9419207 Q.Chen, A.Barragan, V.Fernandez, A.Sundström, M.Schlichtherle, A.Sahlén, J.Carlson, S.Datta, and M.Wahlgren (1998).
Identification of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as the rosetting ligand of the malaria parasite P. falciparum.
  J Exp Med, 187, 15-23.  
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.  
  10082365 T.D.Osslund, R.Syed, E.Singer, E.W.Hsu, R.Nybo, B.L.Chen, T.Harvey, T.Arakawa, L.O.Narhi, A.Chirino, and C.F.Morris (1998).
Correlation between the 1.6 A crystal structure and mutational analysis of keratinocyte growth factor.
  Protein Sci, 7, 1681-1690.  
9634701 W.J.Fairbrother, M.A.Champe, H.W.Christinger, B.A.Keyt, and M.A.Starovasnik (1998).
Solution structure of the heparin-binding domain of vascular endothelial growth factor.
  Structure, 6, 637-648.
PDB codes: 1vgh 2vgh
9843417 Y.Luo, W.Lu, K.A.Mohamedali, J.H.Jang, R.B.Jones, J.L.Gabriel, M.Kan, and W.L.McKeehan (1998).
The glycine box: a determinant of specificity for fibroblast growth factor.
  Biochemistry, 37, 16506-16515.  
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.  
9393669 G.McFadden, and D.Kelvin (1997).
New strategies for chemokine inhibition and modulation: you take the high road and I'll take the low road.
  Biochem Pharmacol, 54, 1271-1280.  
9057819 H.J.Gabius (1997).
Animal lectins.
  Eur J Biochem, 243, 543-576.  
9151776 R.D.Rosenberg, N.W.Shworak, J.Liu, J.J.Schwartz, and L.Zhang (1997).
Heparan sulfate proteoglycans of the cardiovascular system. Specific structures emerge but how is synthesis regulated?
  J Clin Invest, 99, 2062-2070.  
9050848 S.Liu, F.Zhou, M.Höök, and D.D.Carson (1997).
A heparin-binding synthetic peptide of heparin/heparan sulfate-interacting protein modulates blood coagulation activities.
  Proc Natl Acad Sci U S A, 94, 1739-1744.  
9334739 T.R.Transue, A.K.Smith, H.Mo, I.J.Goldstein, and M.A.Saper (1997).
Structure of benzyl T-antigen disaccharide bound to Amaranthus caudatus agglutinin.
  Nat Struct Biol, 4, 779-783.
PDB codes: 1jlx 1jly
9256277 Y.Chen, T.Maguire, R.E.Hileman, J.R.Fromm, J.D.Esko, R.J.Linhardt, and R.M.Marks (1997).
Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate.
  Nat Med, 3, 866-871.  
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
8810913 F.Lustig, J.Hoebeke, G.Ostergren-Lundèn, F.Velge-Roussel, G.Bondjers, U.Olsson, U.Rüetschi, and G.Fager (1996).
Alternative splicing determines the binding of platelet-derived growth factor (PDGF-AA) to glycosaminoglycans.
  Biochemistry, 35, 12077-12085.  
9023055 M.Goldfarb (1996).
Functions of fibroblast growth factors in vertebrate development.
  Cytokine Growth Factor Rev, 7, 311-325.  
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.