1dzd
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HIGH RESOLUTION STRUCTURE OF ACIDIC FIBROBLAST GROWTH FACTOR (27-154), 24 NMR STRUCTURES
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[602115], LADD syndrome OMIM:[602115]
About this StructureAbout this Structure
1DZD is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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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