Solution structure of a biologically active human FGF-1 monomer, complexed to a
hexasaccharide heparin-analogue

exhibits angiogenic and a variety of growth an differentiation activities

Residues 16 to 26 have been added in the molecule studied here.

Solution NMR structure of a human FGF-1 monomer, activated by a hexasaccharide heparin-analogue.

(2R,3S,4S,5R,6R)-3,4,6-trihydroxy-5-sulfooxy-oxane-2-carboxylic acid

[(2S,3R,4R,5S,6R)-6-(hydroxymethyl)-2,4,5-tris(oxidanyl)oxan-3-yl]sulfamic acid

(2R,3S,4S,5R,6R)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid

[(2R,3S,4R,5R,6S)-5-acetamido-3,4,6-trihydroxy-oxan-2-yl]methyl hydrogen sulfate

A shortened genetically engineered form of acidic fibroblast growth factor
(aFGF), that includes amino acids 28-154 of the full-length sequence (154
residues) plus Met in substitution of Leu27, does not induce cell division even
though it is recognized by the cell membrane receptor, triggers the early
mitogenic events, and retains the neuromodulatory, vasoactive, and cardio- and
neuroprotective properties of the native full-length molecule. Taken together,
these properties make this truncated aFGF a promising compound in the treatment
of a wide assortment of neurological and cardiovascular pathologies where aFGF
mitogenic activity is dispensable. Differences in biological activities between
the shortened aFGF and the wild-type form have been attributed to lack of
stability, and to the specific amino acid sequence missing at the N-terminus.
Here we show that this shortened aFGF form has a three-dimensional structure
even more stable than the wild-type protein at the mitogenic assay conditions;
that this structure is similar to that of the wild type except at site 1 of
interaction with the cell membrane receptor; that its lack of mitogenic
activity cannot be attributed to the specific missing sequence; and that the
vasodilatory activity of aFGF seems impaired by alterations of the
three-dimensional structure of site 2 of interaction with the cell membrane
receptor.

Lozano RM, Pineda-Lucena A, Gonzalez C, Angeles Jimenez M, Cuevas P,
Redondo-Horcajo M, Sanz JM, Rico M, Gimenez-Gallego G.
1H NMR structural characterization of a nonmitogenic, vasodilatory,
ischemia-protector and neuromodulatory acidic fibroblast growth factor.
Biochemistry. 2000 May 2;39(17):4982-93.

1H NMR structural characterization of a nonmitogenic, vasodilatory, ischemia-protector and neuromodulatory acidic fibroblast growth factor.

The first direct NMR determination of the conformation of a conformationally
flexible heparin-like hexasaccharide bound to a key receptor, FGF-1, is
described. The determination has been based on the use of a 13C-labeled protein
and a regular 12C sugar. FGF-1 recognizes several conformations of the iduronic
moieties of the hexasaccharide. Therefore, this case is different than that
described for the controversial recognition of heparin-like saccharides by
AT-III, which seems to recognize just one conformation of the iduronic acid
residues.

Canales A, Angulo J, Ojeda R, Bruix M, Fayos R, Lozano R, Gimenez-Gallego G,
Martin-Lomas M, Nieto PM, Jimenez-Barbero J.
Conformational flexibility of a synthetic glycosylaminoglycan bound to a
fibroblast growth factor. FGF-1 recognizes both the (1)C(4) and (2)S(O)
conformations of a bioactive heparin-like hexasaccharide.
J. Am. Chem. Soc. 2005 Apr 27;127(16):5778-9.

Journal of the American Chemical Society
Conformational flexibility of a synthetic glycosylaminoglycan bound to a fibroblast growth factor. FGF-1 recognizes both the (1)C(4) and (2)S(O) conformations of a bioactive heparin-like hexasaccharide.

Synthetic heparin-like hexasaccharide in which the sulfate groups are
exclusively oriented on a single side of the typical helical structure
of glycosylaminoglycans.

Heparin-Linked Biologically-Active Dimer Of Fibroblast Growth Factor

Ligand-binding Portion Of Fibroblast Growth Factor Receptor 2 In Complex With Fgf1

High Resolution Structure Of Acidic Fibroblast Growth Factor. Mutant Fgf-4-ala-(23-154), 24 Nmr Structures

High Resolution Structure Of Acidic Fibroblast Growth Factor (27-154), 24 Nmr Structures

Crystal Structure Of A Ternary Fgf1-Fgfr2-Heparin Complex

Crystal Structure Of Fgf1 In Complex With The Extracellular Ligand Binding Domain Of Fgf Receptor 1 (Fgfr1)

A Complex Between Acidic Fibroblast Growth Factor And 5- Amino-2-Naphthalenesulfonate

Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form With Amino Terminal His Tag.

Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form With Amino Histidine Tag And Leu 73 Replaced By Val (L73v)

Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form With Amino Terminal His Tag And Val 109 Replaced By Leu (v109l)

Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form With Amino Terminal His Tag And Leu 73 Replaced By Val And Val 109 R

Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form With Amino Terminal His Tag And Leu 44 Replaced By Phe And Leu 73 Re

Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form With Amino Terminal His Tag And Leu 44 Replaced By Phe (L44f)

Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form With Amino Terminal His Tag And Cys 117 Replaced With Val (C117v)

Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form With Amino Terminal His Tag With His93 Replaced By Gly (H93g)

Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form With Amino Terminal His Tag With Asn106 Replaced By Gly (N106g)

Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form With Amino Terminal His Tag And Leu 44 Replaced With Phe (L44f), Leu

Human Acidic Fibroblast Growth Factor. 140 Amino Acid Form With Amino Terminal His Tag And Leu111 Replaced With Ile (L111i)

Crystal Structure Of Fgf-1, S50gV51G MUTANT

Human Acidic Fibroblast Growth Factor (Hafgf-1) At 1.10 Angstrom Resolution (140 Amino Acid Form)

Nmr Study Of Acid Fibroblast Growth Factor Bound To 1,3,6- Naphthalene Trisulphonate, 26 Structures

Crystal Structure Of The 3 Ig Form Of Fgfr3c In Complex With Fgf1

Crystal Structure Of Gly19 Deletion Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of Glu60 Deletion Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of Gly19 And Glu60 Deletion Mutant Of Human Acidic Fibroblast Growth Factor

2.0 Angstrom X-Ray Structure Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of Fgf-1, S17tN18TG19 DELETION MUTANT

Solution Structure Of A Biologically Active Human Fgf-1 Monomer, Complexed To A Hexasaccharide Heparin-Analogue

Crystal Structure Of Lys12cysCYS117VAL MUTANT OF HUMAN Acidic Fibroblast Growth Factor At 1.60 Angstrom Resolution

Crystal Structure Of Lys12thrCYS117VAL MUTANT OF HUMAN Acidic Fibroblast Growth Factor At 1.65 Angstrom Resolution

Crystal Structure Of Lys12valCYS117VAL MUTANT OF HUMAN Acidic Fibroblast Growth Factor At 1.60 Angstrom Resolution

Crystal Structure Of Lys12valASN95VALCYS117VAL MUTANT OF Human Acidic Fibroblast Growth Factor At 1.70 Angstrom Resolution

Acidic Fibroblast Growth Factor Solution Structure In The Fgf-1-C2a Binary Complex: Key Component In The Fibroblast Growthfacto

Fgf-1-C2a Binary Complex Structure: A Key Component In The Fibroblast Growthfactor Non-Classical Pathway

Solution Structure Of Human Acidic Fibroblast Growth Factor In Complex With Anti-Angiogenic Drug Inositol Hexaphosphate (Ip6)

Fgf1-S100a13 Complex Structure: Key Component In Non-Classic Way Of Fgf1

The Fgf1-S100a13-C2a Hetero-Hexameric Complex Structure: A C In The Non-Classical Pathway For Fgf1 Secretion

Human Fibroblast Growth Factor-1 (140 Amino Acid Form) With Cys117valPRO134CYS MUTATIONS

Crystal Structure Of Highly Stable Mutant Q40p/s47i/h93g Of Human Fibroblast Growth Factor-1

Solution Structure Of Human Acidic Fibroblast Growth Factor (Afgf) In The Presence Of A Protein Stabilizer Ndsb-New

Crystal Structure Of The Rat Fgf1-sucrose Octasulfate (sos) Complex

Crystal Structure Of L26nD28NH93G MUTANT OF HUMAN ACIDIC Fibroblast Growth Factor

Crystal Structure Of L26d Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of D28a Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of L26nD28A MUTANT OF HUMAN ACIDIC Fibroblast Growth Factor

Crystal Structure Of D70aH93G MUTANT OF HUMAN ACIDIC Fibroblast Growth Factor

Crystal Structure Of K112nN114A MUTANT OF HUMAN ACIDIC Fibroblast Growth Factor

Crystal Structure Of K112n Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of L26n Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of L26a Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of K12vL26DD28A MUTANT OF HUMAN ACIDIC Fibroblast Growth Factor

fibroblast growth factor 1 [Pongo abelii]

Crystal Structure Of L26aD28N MUTANT OF HUMAN ACIDIC Fibroblast Growth Factor

Crystal Structure Of L26dD28N MUTANT OF HUMAN ACIDIC Fibroblast Growth Factor

Crystal Structure Of Human Fibroblast Growth Factor-1 With Mutations Glu81ala And Lys101ala

Crystal Structure Of Human Fibroblast Growth Factor-1 With Mutations Glu81ala, Glu82asn And Lys101ala

Crystal Structure Of Human Fibroblast Growth Factor-1 With Mutations Glu81ser And Lys101ala

Crystal Structure Of Human Fibroblast Growth Factor-1 With Mutations Glu81ser, Glu82asn And Lys101ala

Crystal Structure Of 2:2:2 Fgfr2d2:fgf1:sos Complex

Crystal Structure Of L44fC83TC117VF132W MUTANT OF HUMAN Acidic Fibroblast Growth Factor

Crystal Structure Of C117i Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of F85w Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of F132w Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of V31i Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of L44w Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of L44fF132W MUTANT OF HUMAN ACIDIC Fibroblast Growth Factor

Crystal Structure Of C83s Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of C83t Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of C83a Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of K12vC83IC117V MUTANT OF HUMAN ACIDIC Fibroblast Growth Factor

Crystal Structure Of C83v Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of A66c Mutant Of Human Acidic Fibroblast Growth Factor

Crystal Structure Of Rabbit Acidic Fibroblast Growth Factor

Crystal Structure Of Oxidized A66c Mutant Of Human Acidic Fibroblast Growth Factor

Acidic Fibroblast Growth Factor (Fgf-1) Complexed With Gentisic Acid

Acidic Fibroblast Growth Factor (Fgf-1) Complexed With Dobes

Crystal Structure Of Fgf1 Complexed With The Ectodomain Of Fgfr2b Harboring The A172f Pfeiffer Syndrome Mutation

Crystal Structure Of Fgf1 Complexed With The Ectodomain Of Fgfr2b Harboring P253r Apert Mutation

Crystal Structure Of Fgf1 Complexed With The Ectodomain Of Fgfr1c Exhibiting An Ordered Ligand Specificity-Determining Betac'-B

Crystal Structure Analysis Of Fgf1-disaccharide(ni21) Complexes

Crystal Structure Analysis Of Fgf1-disaccharide(ni22) Complex

Crystal Structure Analysis Of Fgf1-disaccharide(ni23) Complex

Crystal Structure Analysis Of Fgf1-disaccharide(ni24) Complex

Low Resolution Crystal Structure Of The Fgfr2d2d3/fgf1/sr128545 Complex

fibroblast growth factor 1 [synthetic construct]

acidic fibroblast growth factor [Sus scrofa]

acidic fibroblast growth factor [Homo sapiens]

sp1 fibroblast growth factor 1 fusion protein [synthetic construct]

heparin-binding growth factor 1, partial [Homo sapiens]

beta-endothelial cell growth factor [Homo sapiens]

acidic fibroblast growth factor, partial [Homo sapiens]

fibroblast growth factor 1 isoform 1 precursor [Homo sapiens]

RecName: Full=Fibroblast growth factor 1; Short=FGF-1; AltName: Full=Acidic fibroblast growth factor; Short=aFGF; AltName: Full

Simulated annealing, restrained molecular dynamics

The software performs acquisition in Bruker spectrometers and it can also be
used for processing NMR experiments adquired in Bruker or Varian spectrometers.

The software performs acquisition and processing in Varian spectrometers.

This program helps visualization and assignment of 2D and 3D NMR spectra.
Bartels C., Xia T., Billeter M., Guntert P. and Wuthrich K. (1995) J. Biol. NMR
6, 1-10. The program XEASY for computer-supported NMR spectral analysis of
biological macromolecules.

This program yields a collection of protein structures that fit the 1H-1H
distance constraints experimentally obtained.
Guntert P., Mumenthaler C. and Wuthrich K. (1997) J. Mol. Biol. 273, 283-298.
Torsion angle dynamics for NMR structure calculation with the new program
DYANA.

The programs used from this package perform molecular dynamics calculations on
protein structures and complexes between proteins and other biomolecules. They
also convert dyana-format pdb files into amber-format pdb files.
Pearlman D. A., Case D. A., Caldwell J. W., Cheatham T. E., DeBolt S., Ross W.
S., Ferguson D., Seibel G. L., and Kollman P. A. (1995) Comp. Phys. Commun. 91,
1-41. AMBER, a package of computer programs for applying molecular mechanics,
normal mode analysis, molecular dynamics and free energy calculations to
simulate the structural and energetic properties of molecules.