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pubmed-article:7803405pubmed:abstractTextThe amino-terminal fragment (ATF) of urokinase-type plasminogen activator (u-PA) is a two-domain protein which consists of a kringle and a growth factor domain (GFD). The dynamics of uniformly 15N-labeled ATF was examined by measuring the longitudinal (T1) and transverse (T2) 15N relaxation times and heteronuclear NOEs. The data were interpreted in terms of the model-independent spectral density function. The GFD was found to exhibit a high degree of anisotropy, whereas the kringle domain of ATF undergoes isotropic reorientation. This difference in anisotropy is best explained by the two domains moving independently such as differently shaped beads on a string. With the exception of the N- and C-terminal regions of the protein, the most flexible region of ATF was the seven-residue omega loop (N22-I28) of the GFD which has been implicated in the binding of u-PA to its receptor. The amides of the linker region between the domains displayed high values of the order parameter, indicating restricted motion on the picosecond time scale. This is in contrast to the flexible linker of calmodulin [Barbato et al. (1992) Biochemistry 31, 5269-5278], which displayed low values of S2 and unrestricted motion in the linker region.lld:pubmed
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pubmed-article:7803405pubmed:authorpubmed-author:HansenA PAPlld:pubmed
pubmed-article:7803405pubmed:authorpubmed-author:FesikS WSWlld:pubmed
pubmed-article:7803405pubmed:authorpubmed-author:PetrovA BABlld:pubmed
pubmed-article:7803405pubmed:authorpubmed-author:MeadowsR PRPlld:pubmed
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pubmed-article:7803405pubmed:pagination15418-24lld:pubmed
pubmed-article:7803405pubmed:dateRevised2008-11-21lld:pubmed
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pubmed-article:7803405pubmed:year1994lld:pubmed
pubmed-article:7803405pubmed:articleTitleBackbone dynamics of a two-domain protein: 15N relaxation studies of the amino-terminal fragment of urokinase-type plasminogen activator.lld:pubmed
pubmed-article:7803405pubmed:affiliationPharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Ilinois 60064.lld:pubmed
pubmed-article:7803405pubmed:publicationTypeJournal Articlelld:pubmed