A theoretical study of the principles regulating the specificity for Al(III) against Mg(II) in protein cavities

Rezabal, Elixabete; Mercero, José M.; López, Xabier; Ugalde, Jesus M.

doi:10.1016/j.jinorgbio.2007.06.010

Cited by 33 publications

(28 citation statements)

References 42 publications

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“…The characterization of Al(III) speciation in biosystems is a complex problem, and theoretical calculations can help shed light on the different Al-complexes formed in aqueous solution at equilibrium [8][9][10][11][12][13][14][15][16][17][18][19] and non-equilibrium [20,21]. In this sense, calculations show [9,18,22] that Al 3+ can deeply alter the structural and chemical properties of bound ligands, pointing to a significant interference of Al 3+ in biological systems.…”

Section: Introductionmentioning

confidence: 99%

“…For example, aluminium has been shown to replace magnesium in the catalytic sites of regulatory enzymes [3,4,[25][26][27], and model calculations have shown that Al 3+ can displace Mg 2+ in carboxylic-rich buried metal sites [13][14][15]18,23]. Aluminum also competes effectively with ferric iron, due to its same charge and similar ionic radii with their favoured octahedral coordination [24].…”

Section: Introductionmentioning

confidence: 99%

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Pro-oxidant activity of aluminum: Promoting the Fenton reaction by reducing Fe(III) to Fe(II)

Ruipérez

Mujika

Ugalde

et al. 2012

Journal of Inorganic Biochemistry

112

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pro-oxidant activity of aluminum: Promoting the Fenton reaction by reducing Fe(III) to Fe(II)

Ruipérez

Mujika

Ugalde

et al. 2012

Journal of Inorganic Biochemistry

112

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“…The most interesting building blocks with respect to aluminium interaction are amino acid side chains commonly present in metal-ion binding sites, and phosphates ubiquitously present in DNA, RNA, ATP, etc [12]. A first step towards this goal in the group was carried out by Mercero [13–18] and then Rezabal [19–21], who analyzed a series of clusters in which aluminium interacts with various amino acid sidechains in a proteic environment. The protein environments were modeled with the so-called cluster-continuum approach [22, 23].…”

Section: Aluminium Interaction With Biomolecular Building Blocks:mentioning

confidence: 99%

Aluminium in Biological Environments: A Computational Approach

Mujika

Rezabal

Mercero

et al. 2014

Computational and Structural Biotechnology Journal

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The increased availability of aluminium in biological environments, due to human intervention in the last century, raises concerns on the effects that this so far “excluded from biology” metal might have on living organisms. Consequently, the bioinorganic chemistry of aluminium has emerged as a very active field of research. This review will focus on our contributions to this field, based on computational studies that can yield an understanding of the aluminum biochemistry at a molecular level. Aluminium can interact and be stabilized in biological environments by complexing with both low molecular mass chelants and high molecular mass peptides. The speciation of the metal is, nonetheless, dictated by the hydrolytic species dominant in each case and which vary according to the pH condition of the medium. In blood, citrate and serum transferrin are identified as the main low molecular mass and high molecular mass molecules interacting with aluminium. The complexation of aluminium to citrate and the subsequent changes exerted on the deprotonation pathways of its tritable groups will be discussed along with the mechanisms for the intake and release of aluminium in serum transferrin at two pH conditions, physiological neutral and endosomatic acidic. Aluminium can substitute other metals, in particular magnesium, in protein buried sites and trigger conformational disorder and alteration of the protonation states of the protein's sidechains. A detailed account of the interaction of aluminium with proteic sidechains will be given. Finally, it will be described how alumnium can exert oxidative stress by stabilizing superoxide radicals either as mononuclear aluminium or clustered in boehmite. The possibility of promotion of Fenton reaction, and production of hydroxyl radicals will also be discussed.

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“…Tautomerism interconverting 1(4-X) and 1(5-X) species was considered for these compounds. [48,49] QTAIM atomic electron populations [N(Ω)] and electron densities at bond critical points [BCP; ρ b (r)], were obtained with the AIM-PAC package of programs. This computational level was found to provide similar results to those obtained with MP2 in previous work on indole protonation.…”

Section: Computational Detailsmentioning

confidence: 99%

An Electron‐Density‐Based Study on the Ionic Reactivity of 1,3‐Azoles

et al. 2012

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Basic processes for the ionic chemistry of 1,3‐azoles (protonation, nitration, hydride addition, and deprotonation) have been studied by analyzing B3LYP/6‐311++G(2d,2p) 6d electron densities using the Quantum Theory of Atoms in Molecules (QTAIM) and delocalization indices in the gas phase and in aqueous solution modeled with the Polarizable Continuum Model (PCM) method. The most stable protonation site is N3 in all cases, and this takes place without a significant change in electron delocalization, whereas C5 is the preferred site for electrophilic substitution. Activating and deactivating effects on the carbon atoms of the imidazole ring were tested by analyzing the variation of atomic properties introduced by amino and nitro substituents, respectively. The largest activation was observed for C5 in 4‐aminoimidazole. C2 is the most favored site for hydridation in all 1,3‐azoles, which always results in loss of ring planarity and reduced electron delocalization in the ring. PCM calculations allow the experimentally observed preferred deprotonation C‐site in water for these compounds to be modeled and reproduced. In all anions, QTAIM charges do not keep in line with the resonance forms; whereas QTAIM describes deprotonated carbon atoms as positive or nearly neutral in the gas phase, they should display negative charge according to the resonance model.

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A theoretical study of the principles regulating the specificity for Al(III) against Mg(II) in protein cavities

Cited by 33 publications

References 42 publications

Pro-oxidant activity of aluminum: Promoting the Fenton reaction by reducing Fe(III) to Fe(II)

Pro-oxidant activity of aluminum: Promoting the Fenton reaction by reducing Fe(III) to Fe(II)

Aluminium in Biological Environments: A Computational Approach

An Electron‐Density‐Based Study on the Ionic Reactivity of 1,3‐Azoles

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