Isoergonic Cooperativity in Glutamate Dehydrogenase Complexes:  A New Form of Allostery

Fisher, Harvey F.; Tally, Jon

doi:10.1021/bi9708388

Cited by 21 publications

(12 citation statements)

References 13 publications

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“…Larger differences are observed for the enthalpy and entropy changes, particularly between βlg 1 and the first site of βlg 2 . Accordingly, βlg exhibits properties that fall near the threshold of isoergonic cooperativity (Fisher and Tally, ). As a result of reciprocal effects, ligand binding favors subunit monomerization.…”

Section: Discussionsupporting

confidence: 88%

Ligand binding and self‐association cooperativity of β‐lactoglobulin

Gutiérrez-Magdaleno

Bello

Portillo-Téllez

et al. 2013

J of Molecular Recognition

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Unlike most small globular proteins, lipocalins lack a compact hydrophobic core. Instead, they present a large central cavity that functions as the primary binding site for hydrophobic molecules. Not surprisingly, these proteins typically exhibit complex structural dynamics in solution, which is intricately modified by intermolecular recognition events. Although many lipocalins are monomeric, an increasing number of them have been proven to form oligomers. The coupling effects between self-association and ligand binding in these proteins are largely unknown. To address this issue, we have calorimetrically characterized the recognition of dodecyl sulfate by bovine β-lactoglobulin, which forms weak homodimers at neutral pH. A thermodynamic analysis based on coupled-equilibria revealed that dimerization exerts disparate effects on the ligand-binding capacity of β-lactoglobulin. Protein dimerization decreases ligand affinity (or, reciprocally, ligand binding promotes dimer dissociation). The two subunits in the dimer exhibit a positive, entropically driven cooperativity. To investigate the structural determinants of the interaction, the crystal structure of β-lactoglobulin bound to dodecyl sulfate was solved at 1.64 Å resolution.

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Section: Discussionsupporting

confidence: 88%

Ligand binding and self‐association cooperativity of β‐lactoglobulin

Gutiérrez-Magdaleno

Bello

Portillo-Téllez

et al. 2013

J of Molecular Recognition

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“…a reciprocating subunit mechanism). Such a mechanism was used to describe anomalous steady-state kinetics [47] and has been recently explored using microcalorimetery [48,49]. The latter studies suggest that the entropy and enthalpy changes upon coenzyme binding are dependent upon enzyme saturation.…”

Section: Negative Cooperativitymentioning

confidence: 99%

The structure of bovine glutamate dehydrogenase provides insights into the mechanism of allostery

1999

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We propose that the antenna serves as an intersubunit communication conduit during negative cooperativity and allosteric regulation. GTP and NADH inhibit GDH by keeping the catalytic cleft in a closed conformation. In contrast, ADP probably binds to the back of the NAD(+)-binding domain and activates the enzyme by keeping the catalytic cleft open. Extensive contacts between antennae within the crystal lattice may represent hexamer interactions in solution and, perhaps, with other enzymes within the mitochondrial matrix.

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“…The data above demonstrate that TS exhibits “silent” or “isoergonic” allostery (Fisher and Tally, 1997 ; Fisher, 2012 ) with respect to dUMP and cofactor binding. In otherwords, the two binding events have similar affinities, but differ in ΔH, ΔS, and/or ΔC P .…”

Section: Quantifying Substrate Binding Cooperativity In Ectsmentioning

confidence: 89%

Thermodynamic and NMR Assessment of Ligand Cooperativity and Intersubunit Communication in Symmetric Dimers: Application to Thymidylate Synthase

Lee

Sapienza

2018

Front. Mol. Biosci.

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Thymidylate synthase (TS) is a homodimeric enzyme with evidence for negative regulation of one protomer while the other protomer acts on substrate, so called half-the-sites reactivity. The mechanisms by which multisubunit allosteric proteins communicate between protomers is not well understood, and the simplicity of dimeric systems has advantages for observing conformational and dynamic processes that functionally connect distance-separated active sites. This review considers progress in overcoming the inherent challenges of accurate thermodynamic and atomic-resolution characterization of interprotomer communication mechanisms in symmetric protein dimers, with TS used as an example. Isothermal titration calorimetry (ITC) is used to measure ligand binding cooperativity, even in cases where the two binding enthalpies are similar, and NMR spectroscopy is used to detect site-specific changes occurring in the two protomers. The NMR approach makes use of mixed-labeled dimers, enabling protomer-specific detection of signals in the singly ligated state. The rich informational content of the NMR signals from the singly ligated state, relative to the apo and saturated states, requires new considerations that do not arise in simple cases of 1:1 protein-ligand interactions.

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Isoergonic Cooperativity in Glutamate Dehydrogenase Complexes: A New Form of Allostery

Cited by 21 publications

References 13 publications

Ligand binding and self‐association cooperativity of β‐lactoglobulin

Ligand binding and self‐association cooperativity of β‐lactoglobulin

The structure of bovine glutamate dehydrogenase provides insights into the mechanism of allostery

Thermodynamic and NMR Assessment of Ligand Cooperativity and Intersubunit Communication in Symmetric Dimers: Application to Thymidylate Synthase

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