1dzc

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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dzc OCA], [http://www.ebi.ac.uk/pdbsum/1dzc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1dzc RCSB]</span>
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==Overview==
==Overview==
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.
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.
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==Disease==
 
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Known diseases associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602115 602115]], LADD syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602115 602115]]
 
==About this Structure==
==About this Structure==
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[[Category: growth factor]]
[[Category: growth factor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:46:54 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:51:48 2008''

Revision as of 16:51, 30 March 2008


PDB ID 1dzc

Drag the structure with the mouse to rotate
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



HIGH RESOLUTION STRUCTURE OF ACIDIC FIBROBLAST GROWTH FACTOR. MUTANT FGF-4-ALA-(23-154), 24 NMR STRUCTURES


Overview

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.

About this Structure

1DZC is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

1H NMR structural characterization of a nonmitogenic, vasodilatory, ischemia-protector and neuromodulatory acidic fibroblast growth factor., Lozano RM, Pineda-Lucena A, Gonzalez C, Angeles Jimenez M, Cuevas P, Redondo-Horcajo M, Sanz JM, Rico M, Gimenez-Gallego G, Biochemistry. 2000 May 2;39(17):4982-93. PMID:10819962

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