Beryllium binding at neutral pH: The importance of the motif

Keizer, Timothy S.; Sauer, Nancy N.; McCleskey, T. Mark

doi:10.1016/j.jinorgbio.2005.02.017

Cited by 21 publications

(13 citation statements)

References 19 publications

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“…To deduce the position of the Be 2+ , we relied on previous analyses of numerous small molecule structures containing Be 2+ coordinated by oxygens, as well as larger protein structures in which an aspartic acid carboxylate has captured BeF 3 . The coordination chemistry of Be 2+ is well documented in these studies (Everest, 1964; Keizer et al, 2005). The high charge density if Be 2+ creates four short, semi-covalent bonds (1.5 to 1.7 Å) to its ligands distributed in a tetrahedral arrangement with bond angles of about 110°.…”

Section: Resultsmentioning

confidence: 75%

Structural Basis of Chronic Beryllium Disease: Linking Allergic Hypersensitivity and Autoimmunity

Clayton

Wang

Crawford

et al. 2014

Cell

106

140

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SUMMARY T cell-mediated hypersensitivity to metal cations is common in humans. How the T cell antigen receptor (TCR) recognizes these cations bound to a major histocompatibility complex (MHC) protein and self-peptide is unknown. Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a debilitating inflammatory lung condition caused by the reaction of CD4 T cells to inhaled beryllium. We show here that the T cell ligand is created when a Be2+ cation becomes buried in an HLA-DP2/peptide complex, where it is coordinated by both MHC and peptide acidic amino acids. Surprisingly, the TCR does not interact with the Be2+ itself, but rather with surface changes induced by the firmly bound Be2+ and an accompanying Na+ cation. Thus, CBD, by creating a new antigen by indirectly modifying the structure of pre-existing self MHC-peptide complex, lies on the border between allergic hypersensitivity and autoimmunity.

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Section: Resultsmentioning

confidence: 75%

Structural Basis of Chronic Beryllium Disease: Linking Allergic Hypersensitivity and Autoimmunity

Clayton

Wang

Crawford

et al. 2014

Cell

106

140

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“…(22) As the ratio of Be:CA was varied (pH = 9) from 0.05:1 to 2:1, the 9 Be NMR remained unchanged with peaks at ∼3.5 and ∼1.9 ppm, indicating two tightly binding Be sites, with the second binding constant significantly higher than the first. At a 2:1 ratio the Be species is soluble above in molar concentrations up to pH 10.…”

Section: Citric Acid Binding Via a Bridging Alcoholmentioning

confidence: 94%

“…(22) Competition experiments showed that tricarballylic acid does not bind beryllium nearly as well as citric acid, suggesting that more than the carboxylates are involved in effective binding of Be 2+ .…”

Section: Citric Acid Binding Via a Bridging Alcoholmentioning

confidence: 99%

Beryllium and Strong Hydrogen Bonds

McCleskey

Scott

2009

Journal of Occupational and Environmental Hygiene

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We compare beryllium to H+ and show that beryllium can displace H+ in many "strong hydrogen bonds" where Be as a "tetrahedral proton" (O-Be-O angle is tetrahedral as opposed to the nearly linear O-H-O angle) is thermodynamically preferred. The strong hydrogen bond provides two advantages. First, the O-X distance in a strong hydrogen bond is in the range 2.4-2.8 A, which brings two oxygen atoms into a predefined chelating binding site for beryllium. Second, the strong hydrogen bond provides a low barrier pathway to displace the proton without breaking a strong covalent O-H bond by shifting the proton to the more acidic site as Be interacts with the basic oxygen. The low barrier to proton transfer associated with a strong hydrogen bond provides a kinetic pathway for Be binding, and the binding strength increases with the increasing basicity of the site as indicated by the pKa. The physiological importance of this type of interaction is demonstrated with the solubility of a variety of Be complexes at pH 7. Based on this concept, new ligands have been designed for Be binding that solubilize Be in phosphate media and can be used as fluorescent imaging agents. Finally, the binding of Be to the iron transport protein transferrin is discussed as it relates to the same type of binding.

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“…We used a combination of 13 C and 9 Be NMR spectroscopy to demonstrate that Be is bound in a 2 : 1 Be : CA ratio. 26 As the ratio of Be : CA was varied (pH = 9) from 0.05 : 1 to 2 : 1 the 9 Be NMR spectrum remained unchanged, with peaks at ~3.5 and ~1.9 ppm. At the 2 : 1 ratio the Be species is soluble above pH 5.9 in molar concentrations.…”

Section: Introductionmentioning

confidence: 94%

“…Further studies comparing a variety of ligands that contained aliphatic alcohols and carboxylic acids that could support Be binding in a 2 : 1 Be : ligand ratio demonstrated the preferred geometry for binding involves a bridging aliphatic alcohol and carboxylates to form a unit consisting of one five-membered and one six-membered ring. 26 Binding and deprotonation of the aliphatic alcohol group in CA is rare, but has been observed in the case of Al 3+. [27][28][29] These results have a significant impact in terms of the potential sites for binding in the body.…”

Section: Introductionmentioning

confidence: 99%

The bioinorganic chemistry and associated immunology of chronic beryllium disease

et al. 2008

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Chronic beryllium disease (CBD) is a debilitating, incurable, and often fatal disease that is caused by the inhalation of beryllium particulates. The growing use of beryllium in the modern world, in products ranging from computers to dental prosthetics (390 tons of beryllium in the US in the year 2000) necessitates a molecular based understanding of the disease in order to prevent and cure CBD. We have investigated the molecular basis of CBD at Los Alamos National Laboratory during the past six years, employing a multidisciplinary approach of bioinorganic chemistry and immunology. The results of this work, including speciation, inhalation and dissolution, and immunology will be discussed.

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Beryllium binding at neutral pH: The importance of the motif

Cited by 21 publications

References 19 publications

Structural Basis of Chronic Beryllium Disease: Linking Allergic Hypersensitivity and Autoimmunity

Structural Basis of Chronic Beryllium Disease: Linking Allergic Hypersensitivity and Autoimmunity

Beryllium and Strong Hydrogen Bonds

The bioinorganic chemistry and associated immunology of chronic beryllium disease

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