Evidence for Conformation Changes Induced by Substrates of Phosphoglucomutase

Yankeelov, John A.; Koshland, Daniel E.

doi:10.1016/s0021-9258(18)97476-4

Cited by 94 publications

(19 citation statements)

References 33 publications

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“…the thiol groups and in the inhibition of catalytic activity. These two parameters were correspondingly greater in the presence of substrate than in its absence (Yankeelov and Koshland, 1965). However, similar results were obtained by these authors when these experiments were repeated with dephospho-PGM.…”

Section: Resultssupporting

confidence: 87%

The Sulfhydryl Groups of Rabbit Muscle Phosphoglucomutase^*

Bocchini¹,

Mr²,

Va³

1967

Biochemistry

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Titration of phosphoglucomutase (PGM) with />hydroxymercuribenzoate (p-HMB) reveals the presence of six SH groups per mole. This agrees with the number of half-cystine residues per mole estimated by amino acid analysis. Consequently, the enzyme has no disulfide bonds. The over-all titration rate is much faster for the dephospho-PGM as compared with the phospho-PGM. This is primarily due to the greater accessibility of the third and the fourth sulfhydryl groups. Glucose 1 -phosphate (G-l-P) accelerates the thiol titration rate of the enzyme only insofar as it converts the phospho to the dephospho form. Similarly, glucose 1,6-diphosphate

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Section: Resultssupporting

confidence: 87%

The Sulfhydryl Groups of Rabbit Muscle Phosphoglucomutase^*

Bocchini¹,

Mr²,

Va³

1967

Biochemistry

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“…There are now a number of examples known where spectral shifts in enzymes are brought about by combination with inhibitors or substrates (Fujioka and Imahori, 1962;Suelter and Melander, 1963;Yankeelov and Koshland, 1965;Moon et al, 1965). These shifts provide some of the strongest evidence for a substrateinduced conformational change, often postulated as an important aspect of the catalytic mechanism (Koshland, 1958).…”

mentioning

confidence: 99%

The Reactivity toward N-Bromosuccinimide of Tryptophan in Enzymes, Zymogens, and Inhibited Enzymes^*

Spande¹,

Green²,

Witkop³

1966

Biochemistry

114

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“…The key‐lock concept of Emile Fischer from 1894 to understand the formation of the ligand‐receptor complex (L‐R) is a fundamental pillar of medicinal chemistry. This initial concept was modified and correctly adapted by Daniel Koshland's theory of induced fit, [ 1–5 ] which allowed us to understand the dynamic nature of this process. The development of the macromolecular perturbation theory of Belleau [ 6,7 ] and the activation‐aggregation theory of Changeux and co‐workers [ 8 ] and Karlin [ 9 ] has allowed us to understand even better the complexity of this essential process for medicinal chemistry at molecular level.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the conformational space of the active site of D₂ dopamine receptor. Scope and limitations of the standard docking methods

et al. 2022

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We report here for the first time the potential energy surfaces (PES) of phenyletilamine (PEA) and meta‐tyramine (m‐OH‐PEA) at the D2 dopamine receptor (D2DR) binding site. PESs not only allow us to observe all the critical points of the surface (minimums, maximums, and transition states), but also to note the ease or difficulty that each local minima have for their conformational inter‐conversions and therefore know the conformational flexibility that these ligands have in their active sites. Taking advantage of possessing this valuable information, we analyze how accurate a standard docking study is in these cases. Our results indicate that although we have to be careful in how to carry out this type of study and to consider performing some extra‐simulations, docking calculations can be satisfactory. In order to analyze in detail the different molecular interactions that are stabilizing the different ligand‐receptor (L‐R) complexes, we carried out quantum theory of atoms in molecules (QTAIM) computations and NMR shielding calculations. Although some of these techniques are a bit tedious and require more computational time, our results demonstrate the importance of performing computational simulations using different types of combined techniques (docking/MD/hybrid QM‐MM/QTAIM and NMR shielding calculations) in order to obtain more accurate results. Our results allow us to understand in details the molecular interactions stabilizing and destabilizing the different L‐R complexes reported here. Thus, the different activities observed for dopamine (DA), m‐OH‐PEA, and PEA can be clearly explained at molecular level.

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Evidence for Conformation Changes Induced by Substrates of Phosphoglucomutase

Cited by 94 publications

References 33 publications

The Sulfhydryl Groups of Rabbit Muscle Phosphoglucomutase^*

The Sulfhydryl Groups of Rabbit Muscle Phosphoglucomutase^*

The Reactivity toward N-Bromosuccinimide of Tryptophan in Enzymes, Zymogens, and Inhibited Enzymes^*

Evaluating the conformational space of the active site of D₂ dopamine receptor. Scope and limitations of the standard docking methods

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Evidence for Conformation Changes Induced by Substrates of Phosphoglucomutase

Cited by 94 publications

References 33 publications

The Sulfhydryl Groups of Rabbit Muscle Phosphoglucomutase*

The Sulfhydryl Groups of Rabbit Muscle Phosphoglucomutase*

The Reactivity toward N-Bromosuccinimide of Tryptophan in Enzymes, Zymogens, and Inhibited Enzymes*

Evaluating the conformational space of the active site of D2 dopamine receptor. Scope and limitations of the standard docking methods

Contact Info

Product

Resources

About

The Sulfhydryl Groups of Rabbit Muscle Phosphoglucomutase^*

The Sulfhydryl Groups of Rabbit Muscle Phosphoglucomutase^*

The Reactivity toward N-Bromosuccinimide of Tryptophan in Enzymes, Zymogens, and Inhibited Enzymes^*

Evaluating the conformational space of the active site of D₂ dopamine receptor. Scope and limitations of the standard docking methods