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PDBsum entry 3k1x

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protein ligands Protein-protein interface(s) links
Hormone PDB id
3k1x
Jmol PyMol
Contents
Protein chains
(+ 0 more) 130 a.a. *
Ligands
DBX ×2
Waters ×154
* Residue conservation analysis
PDB id:
3k1x
Name: Hormone
Title: Acidic fibroblast growth factor (fgf-1) complexed with dobes
Structure: Heparin-binding growth factor 1. Chain: a, b, c, d, e, f. Fragment: heparin-binding, unp residues 24-153. Synonym: hbgf-1, acidic fibroblast growth factor, afgf, bet endothelial cell growth factor, ecgf-beta. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.98Å     R-factor:   0.230     R-free:   0.290
Authors: A.Romero,I.S.Fernandez,G.Gimenez-Gallego
Key ref: I.S.Fernández et al. (2010). Gentisic acid, a compound associated with plant defense and a metabolite of aspirin, heads a new class of in vivo fibroblast growth factor inhibitors. J Biol Chem, 285, 11714-11729. PubMed id: 20145243
Date:
29-Sep-09     Release date:   02-Feb-10    
PROCHECK
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 Headers
 References

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

 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     fibroblast growth factor receptor binding     2 terms  

 

 
J Biol Chem 285:11714-11729 (2010)
PubMed id: 20145243  
 
 
Gentisic acid, a compound associated with plant defense and a metabolite of aspirin, heads a new class of in vivo fibroblast growth factor inhibitors.
I.S.Fernández, P.Cuevas, J.Angulo, P.López-Navajas, A.Canales-Mayordomo, R.González-Corrochano, R.M.Lozano, S.Valverde, J.Jiménez-Barbero, A.Romero, G.Giménez-Gallego.
 
  ABSTRACT  
 
Fibroblast growth factors are key proteins in many intercellular signaling networks. They normally remain attached to the extracellular matrix, which confers on them a considerable stability. The unrestrained accumulation of fibroblast growth factors in the extracellular milieu, either due to uncontrolled synthesis or enzymatic release, contributes to the pathology of many diseases. Consequently, the neutralization of improperly mobilized fibroblast growth factors is of clear therapeutic interest. In pursuing described rules to identify potential inhibitors of these proteins, gentisic acid, a plant pest-controlling compound, an aspirin and vegetarian diet common catabolite, and a component of many traditional liquors and herbal remedies, was singled out as a powerful inhibitor of fibroblast growth factors. Gentisic acid was used as a lead to identify additional compounds with better inhibitory characteristics generating a new chemical class of fibroblast growth factor inhibitors that includes the agent responsible for alkaptonuria. Through low and high resolution approaches, using representative members of the fibroblast growth factor family and their cell receptors, it was shown that this class of inhibitors may employ two different mechanisms to interfere with the assembly of the signaling complexes that trigger fibroblast growth factor-driven mitogenesis. In addition, we obtained evidence from in vivo disease models that this group of inhibitors may be of interest to treat cancer and angiogenesis-dependent diseases.
 

 

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