Understanding the fluorescence changes of human plasminogen when it binds the ligand, 6-aminohexanoate: a synthesis

Kornblatt, Jack A.

doi:10.1016/s0167-4838(00)00119-9

Cited by 8 publications

(13 citation statements)

References 46 publications

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“…If we compare these values with the measured thickness of the donut in the crystal structure (ca 5 nm), it indicates that the disk is lying flat on the chip surface. We reiterate that the height data of Figure 3 show that when Str enolase binds to the Pgn surface, the change in height is about 7 nm rather than ∼4 nm; this may be related to the large conformational change occurring when Pgn goes from the closed form to the open form (See Kornblatt [38] and references therein for details).…”

Section: Resultsmentioning

confidence: 84%

The Interaction of Streptococcal Enolase with Canine Plasminogen: The Role of Surfaces in Complex Formation

et al. 2014

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The enolase from Streptococcus pyogenes (Str enolase F137L/E363G) is a homo-octamer shaped like a donut. Plasminogen (Pgn) is a monomeric protein composed of seven discrete separated domains organized into a lock washer. The enolase is known to bind Pgn. In past work we searched for conditions in which the two proteins would bind to one another. The two native proteins in solution would not bind under any of the tried conditions. We found that if the structures were perturbed binding would occur. We stated that only the non-native Str enolase or Pgn would interact such that we could detect binding. We report here the results of a series of dual polarization interferometry (DPI) experiments coupled with atomic force microscopy (AFM), isothermal titration calorimetry (ITC), dynamic light scattering (DLS), and fluorescence. We show that the critical condition for forming stable complexes of the two native proteins involves Str enolase binding to a surface. Surfaces that attract Str enolase are a sufficient condition for binding Pgn. Under certain conditions, Pgn adsorbed to a surface will bind Str enolase.

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Section: Resultsmentioning

confidence: 84%

The Interaction of Streptococcal Enolase with Canine Plasminogen: The Role of Surfaces in Complex Formation

et al. 2014

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“…Plasminogen is kept in a closed conformation via an intramolecular interaction between the N-terminal tail domain and kringle V (27). ⑀-ACA replaces the internal ligand and leads to a transition from a closed to open conformation, resulting in a change in tryptophan fluorescence (28), an increase in the radius of gyration (18), and an enhancement of tPA-or uPA-mediated plasminogen activation to plasmin (29). Binding of plasminogen to fibrin, an important cofactor for plasminogen activation, has been postulated to elicit this conformational change (30).…”

Section: Resultsmentioning

confidence: 99%

A Ligand-induced Conformational Change in Apolipoprotein(a) Enhances Covalent Lp(a) Formation

Becker

Webb

Chitayat

et al. 2003

Journal of Biological Chemistry

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Lipoprotein(a) (Lp(a)) assembly proceeds via a twostep mechanism in which initial non-covalent interactions between apolipoprotein(a) (apo(a)) and low density lipoprotein precede disulfide bond formation. In this study, we used analytical ultracentrifugation, differential scanning calorimetry, and intrinsic fluorescence to demonstrate that in the presence of the lysine analog ⑀-aminocaproic acid, apo(a) undergoes a substantial conformational change from a "closed" to an "open" structure that is characterized by an increase in the hydrodynamic radius (ϳ10%), an alteration in domain stability, as well as a decrease in tryptophan fluorescence. Although ⑀-aminocaproic acid is a well characterized inhibitor of the non-covalent interaction between apo(a) and low density lipoprotein, we report the novel observation that this ligand at low concentrations (100 M-1 mM) significantly enhances covalent Lp(a) assembly by altering the conformation of apo(a). We developed a model for the kinetics of Lp(a) assembly that incorporates the conformational change as a determinant of the efficiency of the process; this model quantitatively explains our experimental observations. Interestingly, an analogous conformational change has been previously described for plasminogen resulting in an increase in the hydrodynamic radius, an increase in tryptophan fluorescence, and an acceleration of the rate of plasminogen activation. Although the functions of apo(a) and plasminogen have diverged considerably, elements of structural and conformational homology have been retained leading to similar regulation of two unrelated biological processes.

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“…When it binds it causes the plasminogen to open and change its hydrodynamic properties [24], [37]. The 6-AH can bind to four (1,2,4,5) of the five kringles, each of which has a different binding coefficient [38]; it is only on binding to kringle 5 that the protein opens [39]. While ANS enhances the rate at which the plasminogen precipitates, 6-AH inhibits the precipitation reaction as shown in Figure 5.…”

Section: Resultsmentioning

confidence: 99%

Reduction of Canine Plasminogen Leads to an Expanded Molecule which Precipitates

Kornblatt

2009

PLoS ONE

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Canine plasminogen is made up of seven domains. In each domain there are several cysteines that are linked by disulfide bonds. Reduction of a limited number of the cystines destabilizes the protein such that it precipitates. The bond or bonds that are broken provide about 14 kcal of stabilization energy. Circular dichroism and dynamic light scattering indicate that there is probably an intermediate that is formed prior to precipitation and that the intermediate is somewhat larger than the compact form of plasminogen.

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Understanding the fluorescence changes of human plasminogen when it binds the ligand, 6-aminohexanoate: a synthesis

Cited by 8 publications

References 46 publications

The Interaction of Streptococcal Enolase with Canine Plasminogen: The Role of Surfaces in Complex Formation

The Interaction of Streptococcal Enolase with Canine Plasminogen: The Role of Surfaces in Complex Formation

A Ligand-induced Conformational Change in Apolipoprotein(a) Enhances Covalent Lp(a) Formation

Reduction of Canine Plasminogen Leads to an Expanded Molecule which Precipitates

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