ChemInform Abstract: Elucidation of the Structure of Pharmacologically Active Magnesium L‐Aspartate Complexes.

Schmidbaur, Hubert; Muêller, G.; Riede, Jürgen; Manninger, Gebhard; Helbig, J.

doi:10.1002/chin.198712270

Cited by 4 publications

(5 citation statements)

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“…This might be caused by the relatively high desolvation energy of a hydrated Mg 2+ ion. Anyway, crystal structures of small organic molecules show first [67,68] and second coordination spheres [69], while protein complexes show stable Mg 2+ binding sites only in first coordination spheres, buried in the protein interior, as discussed elsewhere [65,66]. To clarify if the Mg 2+ ion is coordinated in a first or second coordination sphere, we calculated the solvation free energy of the Mg 2+ ion in water, the second sphere and the first sphere, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…To determine if a second coordination sphere of Mg 2+ without being connected to a first coordination sphere in proteins has been found previously, we looked into the literature, but did not find any Mg 2+ second coordination sphere caused by proteins in absence of a first sphere ion coordination [65,66]. However, crystal structures of small organic compounds, Mg-L-Asp [67], Mg(L-AspH)(D-AspH) [68] and Magnesium Bis[orotate(− I)] Octahydrata [69] have been shown to bind Mg 2+ ions in first or second coordination sphere, respectively. While in the first sphere of Mg-LAsp coordination the nitrogen lone pair coordinates the Mg 2+ ion (denoting that the backbone nitrogen is deprotonated and thus donating a favorable interaction to the Mg 2+ ion) the coordination in the first sphere complex from Mg(L-AspH)(D-AspH) the Mg 2+ ion is Although we found the second coordination sphere of the Mg 2+ ion in the above MD simulations of the ε subunit from B. subtilis, this could be due to a finite time of the simulation.…”

Section: The Mg 2+ Binding Site Derived By Conventional MD Simulationsmentioning

confidence: 95%

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On the Mg2+ binding site of the ε subunit from bacterial F-type ATP synthases

Krah

Takada

2015

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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F-type ATP synthases, central energy conversion machines of the cell synthesize adenosine triphosphate (ATP) using an electrochemical gradient across the membrane and, reversely, can also hydrolyze ATP to pump ions across the membrane, depending on cellular conditions such as ATP concentration. To prevent wasteful ATP hydrolysis, mammalian and bacterial ATP synthases possess different regulatory mechanisms. In bacteria, a low ATP concentration induces a conformational change in the ε subunit from the down- to up-states, which inhibits ATP hydrolysis. Moreover, the conformational change of the ε subunit depends on Mg(2+) concentration in some bacteria such as Bacillus subtilis, but not in others. This diversity makes the ε subunit a potential target for antibiotics. Here, performing molecular dynamics simulations, we identify the Mg(2+) binding site in the ε subunit from B. subtilis as E59 and E86. The free energy analysis shows that the first-sphere bi-dentate coordination of the Mg(2+) ion by the two glutamates is the most stable state. In comparison, we also clarify the reason for the absence of Mg(2+) dependency in the ε subunit from thermophilic Bacillus PS3, despite the high homology to that from B. subtilis. Sequence alignment suggests that this Mg(2+) binding motif is present in the ε subunits of some pathogenic bacteria. In addition we discuss strategies to stabilize an isolated ε subunit carrying the Mg(2+) binding motif by site directed mutagenesis, which also can be used to crystallize Mg(2+) dependent ε subunits in future.

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Section: Discussionmentioning

confidence: 99%

Section: The Mg 2+ Binding Site Derived By Conventional MD Simulationsmentioning

confidence: 95%

On the Mg2+ binding site of the ε subunit from bacterial F-type ATP synthases

Krah

Takada

2015

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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“…Due to difficulties in the preparation of crystalline specimen of such complexes [5,7,8], thorough structural investigations have been performed on metal complexes with the anions of a-L L -aspartic acid and a-L L -glutamic acid [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] (Fig. 1) which can serve as models for the binding of metal ions to proteins.…”

Section: Introductionmentioning

confidence: 99%

Interactions of a β-dipeptide with monovalent metal cations: crystal structures of (anthranoyl)anthranilic acid and its lithium, sodium and thallium salts☆

Wiesbrock

Schmidbaur

2004

Journal of Inorganic Biochemistry

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“…In a series of preparative and structural studies in our own laboratory we have recently investigated the coordination chemistry of the common alkali-metal and alkaline-earth-metal cations with the most important prototypes of amino and hydroxy acids. This program included in particular the α-aspartates and α- and β-glutamates of these metals, but also salicylates and anthranilates. − Several of these compounds are established drugs widely used for the treatment of deficiency disorders. , Complementary literature has been summarized in previous publications.…”

Section: Introductionmentioning

confidence: 99%

Crystal Structures of Rubidium and Cesium Anthranilates and Salicylates

Wiesbrock

Schmidbaur

2003

Inorg. Chem.

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In an attempt to probe a potential template role of the large alkali-metal cations rubidium and cesium in the organization of biorelevant ligands, salicylate and anthranilate complexes of the two elements were prepared and structurally investigated. The studies were also expected to show the marked structural differences compared to the corresponding thallium(I) compounds. Rubidium anthranilate and cesium salicylate could be crystallized as the monohydrates Rb(Anth)(H(2)O) and Cs(Sal)(H(2)O). Both have layer structures containing the cations and the polar groups of the ligands in core domains sandwiched by the aromatic rings above and below. The metal atoms have coordination numbers 7 and 8, respectively, with an irregular coordination sphere made up exclusively of oxygen atoms. Crystalline material with a 1:2 stoichiometry, Cs[H(Anth)(2)], is obtained from aqueous solutions of Cs(Anth) upon absorption of carbon dioxide with concomitant formation of cesium bicarbonate, Cs(HCO(3)). The crystal structure of Cs(HCO(3)) was redetermined to obtain precise benchmark data for cesium carbonates and carboxylates. The cesium hydrogen bisanthranilate also has a layer structure with eight-coordinate cesium atoms. The coordination sphere includes one nitrogen donor atom. The organization of all layer structures appears to be governed mainly by steric effects and electrostatic forces with very little directional influence of the cations. This result suggests that the large alkali metals have no efficient template effect for the organization of biological substrates and can explain the low toxicity of rubidium and cesium salts.

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ChemInform Abstract: Elucidation of the Structure of Pharmacologically Active Magnesium L‐Aspartate Complexes.

Abstract: Magnesium salts of L‐aspartic acid are used in magnesium therapy.

Cited by 4 publications

References 1 publication

On the Mg2+ binding site of the ε subunit from bacterial F-type ATP synthases

On the Mg2+ binding site of the ε subunit from bacterial F-type ATP synthases

Interactions of a β-dipeptide with monovalent metal cations: crystal structures of (anthranoyl)anthranilic acid and its lithium, sodium and thallium salts☆

Crystal Structures of Rubidium and Cesium Anthranilates and Salicylates

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