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Growth factor PDB id
2afg
Jmol
Contents
Protein chains
129 a.a. *
Ligands
SO4 ×4
Waters ×52
* Residue conservation analysis
PDB id:
2afg
Name: Growth factor
Title: 2.0 angstrom x-ray structure of human acidic fibroblast growth factor
Structure: Acidic fibroblast growth factor. Chain: a, b, c, d. Synonym: afg. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Tetramer (from PQS)
Resolution:
2.00Å     R-factor:   0.169    
Authors: M.Blaber,J.Disalvo,K.A.Thomas
Key ref:
M.Blaber et al. (1996). X-ray crystal structure of human acidic fibroblast growth factor. Biochemistry, 35, 2086-2094. PubMed id: 8652550 DOI: 10.1021/bi9521755
Date:
21-Jul-95     Release date:   15-Oct-95    
Supersedes: 1afg
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P05230  (FGF1_HUMAN) -  Heparin-binding growth factor 1
Seq:
Struc: 		155 a.a.
129 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   8 terms 
  Biological process     multicellular organismal development   22 terms 
  Biochemical function     protein binding     6 terms  

 

 
DOI no: 10.1021/bi9521755 Biochemistry 35:2086-2094 (1996)
PubMed id: 8652550  
 
 
X-ray crystal structure of human acidic fibroblast growth factor.
M.Blaber, J.DiSalvo, K.A.Thomas.
 
  ABSTRACT  
 
Fibroblast growth factors (FGFs) are mitogenic and chemotactic agents for a wide variety of cell types and play a primary role in the regulation of angiogenesis. Angiogenesis is involved in a variety of critical physiological events including organogenesis, wound healing, ischemic collateral circulation, and solid tumor growth. High-resolution structural information is key to understanding the mechanism of action of these growth factors. We report here the X-ray crystal structure of human acidic FGF (aFGF), with data extending to 2.0 angstroms resolution. The crystal contains four independent molecules in the asymmetric unit. Each molecule contains a single bound sulfate ion, in similar juxtapositions. The bound sulfate is stabilized through hydrogen-bond interactions with residues Asn 18, Lys 113, and Lys 118 and defines a potential heparin binding site. The hydrogen bond with the N delta 2 moiety of Asn 18 appears to be the most conserved interaction, being similar to those observed for sulfate ion bound to human basic FGF (bFGF) and similar but not identical to interactions observed for bovine aFGF with heparin analogs. Of the added solvent groups, five ordered water molecules are conserved in each of the four independent structures of human aFGF. These water molecules, located at buried positions, provide hydrogen bonding partnerships with several buried polar groups in the core of the protein. A central interior cavity exists in each of the four structures, with sizes ranging from approximately 20 to 50 angstroms3. The cavity sizes appear to be significantly smaller than that observed in the related protein interleukin-1 beta. The region comprising the high affinity FGF receptor binding site is structurally very similar to the corresponding region from human bFGF, whereas the low affinity site is structurally quite different. The results provide a structural basis for the role of the low affinity binding site in FGF receptor discrimination.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21315087 J.Lee, S.I.Blaber, V.K.Dubey, and M.Blaber (2011).
A polypeptide "building block" for the β-trefoil fold identified by "top-down symmetric deconstruction".
  J Mol Biol, 407, 744-763.  
18421160 E.Honjo, T.Tamada, M.Adachi, R.Kuroki, A.Meher, and M.Blaber (2008).
Mutagenesis of the crystal contact of acidic fibroblast growth factor.
  J Synchrotron Radiat, 15, 285-287.  
18697857 H.Yoon, S.I.Blaber, D.M.Evans, J.Trim, M.A.Juliano, I.A.Scarisbrick, and M.Blaber (2008).
Activation profiles of human kallikrein-related peptidases by proteases of the thrombostasis axis.
  Protein Sci, 17, 1998-2007.  
17094138 H.Fan, H.Li, M.Zhang, and C.R.Middaugh (2007).
Effects of solutes on empirical phase diagrams of human fibroblast growth factor 1.
  J Pharm Sci, 96, 1490-1503.  
17823117 H.Yoon, G.Laxmikanthan, J.Lee, S.I.Blaber, A.Rodriguez, J.M.Kogot, I.A.Scarisbrick, and M.Blaber (2007).
Activation profiles and regulatory cascades of the human kallikrein-related peptidases.
  J Biol Chem, 282, 31852-31864.  
18061883 J.Jacobs (2007).
Combating cardiovascular disease with angiogenic therapy.
  Drug Discov Today, 12, 1040-1045.  
16355415 J.Lee, V.K.Dubey, T.Somasundaram, and M.Blaber (2006).
Conversion of type I 4:6 to 3:5 beta-turn types in human acidic fibroblast growth factor: effects upon structure, stability, folding, and mitogenic function.
  Proteins, 62, 686-697.
PDB codes: 1yto 1z2v 1z4s 2aqz
16801558 L.L.Chavez, S.Gosavi, P.A.Jennings, and J.N.Onuchic (2006).
Multiple routes lead to the native state in the energy landscape of the beta-trefoil family.
  Proc Natl Acad Sci U S A, 103, 10254-10258.  
15632285 J.Kim, J.Lee, S.R.Brych, T.M.Logan, and M.Blaber (2005).
Sequence swapping does not result in conformation swapping for the beta4/beta5 and beta8/beta9 beta-hairpin turns in human acidic fibroblast growth factor.
  Protein Sci, 14, 351-359.
PDB codes: 1pzz 1q03 1q04
16081654 V.K.Dubey, J.Lee, and M.Blaber (2005).
Redesigning symmetry-related "mini-core" regions of FGF-1 to increase primary structure symmetry: thermodynamic and functional consequences of structural symmetry.
  Protein Sci, 14, 2315-2323.  
15382229 M.J.Bernett, T.Somasundaram, and M.Blaber (2004).
An atomic resolution structure for human fibroblast growth factor 1.
  Proteins, 57, 626-634.
PDB code: 1rg8
12676958 C.Fernández-Tornero, R.M.Lozano, M.Redondo-Horcajo, A.M.Gómez, J.C.López, E.Quesada, C.Uriel, S.Valverde, P.Cuevas, A.Romero, and G.Giménez-Gallego (2003).
Leads for development of new naphthalenesulfonate derivatives with enhanced antiangiogenic activity: crystal structure of acidic fibroblast growth factor in complex with 5-amino-2-naphthalene sulfonate.
  J Biol Chem, 278, 21774-21781.
PDB code: 1hkn
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
12829501 T.Srimathi, T.K.Kumar, K.M.Kathir, Y.H.Chi, S.Srisailam, W.Y.Lin, I.M.Chiu, and C.Yu (2003).
Structurally homologous all beta-barrel proteins adopt different mechanisms of folding.
  Biophys J, 85, 459-472.  
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.  
11847289 C.Liu, J.A.Gaspar, H.J.Wong, and E.M.Meiering (2002).
Conserved and nonconserved features of the folding pathway of hisactophilin, a beta-trefoil protein.
  Protein Sci, 11, 669-679.  
11847269 J.Kim, S.I.Blaber, and M.Blaber (2002).
Alternative type I and I' turn conformations in the beta8/beta9 beta-hairpin of human acidic fibroblast growth factor.
  Protein Sci, 11, 459-466.
PDB codes: 1k5u 1k5v
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.  
12118009 Y.H.Chi, T.K.Kumar, I.M.Chiu, and C.Yu (2002).
Identification of rare partially unfolded states in equilibrium with the native conformation in an all beta-barrel protein.
  J Biol Chem, 277, 34941-34948.  
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
11296285 N.E.Robinson, and A.B.Robinson (2001).
Prediction of protein deamidation rates from primary and three-dimensional structure.
  Proc Natl Acad Sci U S A, 98, 4367-4372.  
11714927 S.R.Brych, S.I.Blaber, T.M.Logan, and M.Blaber (2001).
Structure and stability effects of mutations designed to increase the primary sequence symmetry within the core region of a beta-trefoil.
  Protein Sci, 10, 2587-2599.
PDB codes: 1jqz 1jt3 1jt4 1jt5 1jt7 1jtc
10830168 A.N.Plotnikov, S.R.Hubbard, J.Schlessinger, and M.Mohammadi (2000).
Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity.
  Cell, 101, 413-424.
PDB codes: 1ev2 1evt
10852713 J.F.Culajay, S.I.Blaber, A.Khurana, and M.Blaber (2000).
Thermodynamic characterization of mutants of human fibroblast growth factor 1 with an increased physiological half-life.
  Biochemistry, 39, 7153-7158.  
10819962 R.M.Lozano, A.Pineda-Lucena, C.Gonzalez, M.Angeles Jiménez, P.Cuevas, M.Redondo-Horcajo, J.M.Sanz, M.Rico, and G.Giménez-Gallego (2000).
1H NMR structural characterization of a nonmitogenic, vasodilatory, ischemia-protector and neuromodulatory acidic fibroblast growth factor.
  Biochemistry, 39, 4982-4993.
PDB codes: 1dzc 1dzd
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.  
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.  
  10548053 N.Nagano, E.G.Hutchinson, and J.M.Thornton (1999).
Barrel structures in proteins: automatic identification and classification including a sequence analysis of TIM barrels.
  Protein Sci, 8, 2072-2084.  
10388772 S.I.Blaber, J.F.Culajay, A.Khurana, and M.Blaber (1999).
Reversible thermal denaturation of human FGF-1 induced by low concentrations of guanidine hydrochloride.
  Biophys J, 77, 470-477.  
9853963 I.Leconte, J.C.Fox, H.S.Baldwin, C.A.Buck, and J.L.Swain (1998).
Adenoviral-mediated expression of antisense RNA to fibroblast growth factors disrupts murine vascular development.
  Dev Dyn, 213, 421-430.  
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.  
8917442 A.Romero, A.Pineda-Lucena, and G.Giménez-Gallego (1996).
X-ray structure of native full-length human fibroblast-growth factor at 0.25-nm resolution.
  Eur J Biochem, 241, 453-461.  
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.