Search results for: Claudia A. Blindauer

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Fatty acids may influence insulin dynamics through modulation of albumin‐Zn²⁺ interactions

Swati Arya, Adam J. Gourley, J. Carlos Penedo, Claudia A. Blindauer, more

Insulin is stored within the pancreas in an inactive Zn²⁺‐bound hexameric form prior to release. Similarly, clinical insulins contain Zn²⁺ and form multimeric complexes. Upon release from the pancreas or upon injection, insulin only becomes active once Zn²⁺ disengages from the complex. In plasma and other extracellular fluids, the majority of Zn²⁺ is bound to human serum albumin (HSA), which plays...

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Metal Ion‐Coordinating Properties in Aqueous Solutions of the Antivirally Active Nucleotide Analogue (S)‐9‐[3‐Hydroxy‐2‐(phosphonomethoxy)propyl]adenine (HPMPA) – Quantification of Complex Isomeric Equilibria

Claudia A. Blindauer, Antonín Holý, Bert P. Operschall, Astrid Sigel, more

European Journal of Inorganic Chemistry > 2019 > 35 > 3892 - 3903

Acyclic nucleoside phosphonates are of medical relevance and deserve detailed chemical characterization. We focus here on (S)‐9‐[3‐hydroxy‐2‐(phosphonomethoxy)propyl]adenine (HPMPA) and include for comparison 9‐[2‐(phosphonomethoxy)ethyl]adenine (PMEA), as well as the nucleobase‐free (phosphonomethoxy)ethane (PME) and (R)‐hydroxy‐2‐(phosphonomethoxy)propane (HPMP). The acidity constants of H₃(HPMPA)...

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Ischemia-modified albumin: Crosstalk between fatty acid and cobalt binding

James P.C. Coverdale, Kondwani G.H. Katundu, Amélie I.S. Sobczak, Swati Arya, more

Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA) > 2018 > 135 > C > 147-157

Myocardial ischemia is difficult to diagnose effectively with still few well-defined biochemical markers for identification in advance, or in the absence of myocardial necrosis. “Ischemia-modified albumin” (IMA), a form of albumin displaying reduced cobalt-binding affinity, is significantly elevated in ischemic patients, and the albumin cobalt-binding (ACB) assay can measure its level indirectly....

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Metal-ion binding properties of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir). A nucleotide analogue with activity against DNA viruses

Claudia A. Blindauer, Astrid Sigel, Bert P. Operschall, Antonín Holý, more

Inorganica Chimica Acta > 2018 > 472 > C > 283-294

The acyclic nucleoside phosphonate (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC; Cidofovir) has been approved for clinical use in antiviral therapy. We determined the acidity constants of H₂(HPMPC)^±, as well as that of the nucleobase-free (hydroxy-2-(phosphonomethoxy)propane (H(HPMP)⁻) (I=0.1M, NaNO₃; 25°C). Given that in vivo nucleotides and their analogues participate in reactions...

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Differential reactivity of closely related zinc(II)-binding metallothioneins from the plant Arabidopsis thaliana

Hasan T. Imam, Claudia A. Blindauer

JBIC Journal of Biological Inorganic Chemistry > 2018 > 23 > 1 > 137-154

The dynamics of metal binding to and transfer from metalloproteins involved in metal homeostasis are important for understanding cellular distribution of metal ions. The dicotyledonous plant Arabidopsis thaliana has two type 4 seed-specific metallothionein homologues, MT4a and MT4b, with likely roles in zinc(II) homeostasis. These two metallothioneins are 84% identical, with full conservation of all...

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Sediment Metal Contamination in the Kafue River of Zambia and Ecological Risk Assessment

Ethel M’kandawire, Kennedy Choongo, John Yabe, Maxwell Mwase, more

Bulletin of Environmental Contamination and Toxicology > 2017 > 99 > 1 > 108-116

Zambia’s Kafue River receives wastes from various sources, resulting in metal pollution. This study determined the degree of contamination of 13 metals (Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Cd, Hg and Pb) in Kafue River sediment and the associated ecological risks at six sites in three different seasons. The level of contamination for most metals showed significant site and seasonal differences...

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O₂‐independent demethylation of trimethylamine N‐oxide by Tdm of Methylocella silvestris

Yijun Zhu, Amira Z. Ksibe, Hendrik Schäfer, Claudia A. Blindauer, more

The FEBS Journal > 283 > 21 > 3979 - 3993

Bacterial trimethylamine N‐oxide (TMAO) demethylase, Tdm, carries out an unusual oxygen‐independent demethylation reaction, resulting in the formation of dimethylamine and formaldehyde. In this study, site‐directed mutagenesis, homology modelling and metal analyses by inorganic mass spectrometry have been applied to gain insight into metal stoichiometry and underlying catalytic mechanism of Tdm of...

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Extent of intramolecular π stacks in aqueous solution in mixed-ligand copper(II) complexes formed by heteroaromatic amines and the anticancer and antivirally active 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG). A comparison with related acyclic nucleotide analogues

Claudia A. Blindauer, Astrid Sigel, Bert P. Operschall, Rolf Griesser, more

Polyhedron > 2016 > 103 > PB > 248-260

The acyclic nucleoside phosphonate (ANP²⁻) 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG) is anticancer and antivirally active. The acidity constants of the threefold protonated H₃(PMEG)⁺ were determined by potentiometric pH titrations (aq. sol.; 25°C; I=0.1M, NaNO₃). Under the same conditions and by the same method, the stability constants of the binary Cu(H;PMEG)⁺ and Cu(PMEG) complexes as well as...

article

The reduced Co²⁺‐binding ability of ischaemia‐modified albumin is unlikely to be because of oxidative modification of the N‐terminus

Alan J. Stewart, Claudia A. Blindauer

Liver International > 35 > 12 > 2622 - 2623

article

Prion infection in cells is abolished by a mutated manganese transporter but shows no relation to zinc

Rachel Pass, Karen Frudd, James P. Barnett, Claudia A. Blindauer, more

Molecular and Cellular Neuroscience > 2015 > 68 > Complete > 186-193

The cellular prion protein has been identified as a metalloprotein that binds copper. There have been some suggestions that prion protein also influences zinc and manganese homeostasis. In this study we used a series of cell lines to study the levels of zinc and manganese under different conditions. We overexpressed either the prion protein or known transporters for zinc and manganese to determine...

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Characterization of Folding Cores in the Cyclophilin A-Cyclosporin A Complex

Jack W. Heal, Stephen A. Wells, Claudia A. Blindauer, Robert B. Freedman, more

Biophysical Journal > 2015 > 108 > 7 > 1739-1746

Determining the folding core of a protein yields information about its folding process and dynamics. The experimental procedures for identifying the amino acids that make up the folding core include hydrogen-deuterium exchange and Φ-value analysis and can be expensive and time consuming. Because of this, there is a desire to improve upon existing methods for determining protein folding cores theoretically...

article

A Canonical EF‐Loop Directs Ca²⁺‐Sensitivity in Phospholipase C‐η2

Petra Popovics, Jin Lu, L. Nadia Kamil, Kevin Morgan, more

Journal of Cellular Biochemistry > 115 > 3 > 557 - 565

Phospholipase C‐η (PLCη) enzymes are a class of phosphatidylinositol 4,5‐bisphosphate‐hydrolyzing enzymes involved in intracellular signaling. PLCη2 can sense Ca²⁺ (stimulated by ∼1 µM free Ca²⁺) suggesting that it can amplify transient Ca²⁺ signals. PLCη enzymes possess an EF‐hand domain composed of two EF‐loops; a canonical 12‐residue loop (EF‐loop 1) and a non‐canonical 13‐residue loop (EF‐loop...

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Allosteric modulation of zinc speciation by fatty acids

James P. Barnett, Claudia A. Blindauer, Omar Kassaar, Siavash Khazaipoul, more

BBA - General Subjects > 2013 > 1830 > 12 > 5456-5464

Serum albumin is the major protein component of blood plasma and is responsible for the circulatory transport of a range of small molecules that include fatty acids, hormones, metal ions and drugs. Studies examining the ligand-binding properties of albumin make up a large proportion of the literature. However, many of these studies do not address the fact that albumin carries multiple ligands (including...

article

Extent of Intramolecular π Stacks in Aqueous Solution in Mixed‐Ligand Copper(II) Complexes Formed by Heteroaromatic Amines and 1‐[2‐(Phosphonomethoxy)ethyl]cytosine (PMEC), a Relative of Antivirally Active Acyclic Nucleotide Analogues (Part 72)^{[1, 2]}

Claudia A. Blindauer, Astrid Sigel, Bert P. Operschall, Antonin Holý, more

Zeitschrift für anorganische und allgemeine Chemie > 639 > 8‐9 > 1661 - 1673

Stability constants of the ternary Cu(Arm)(H;PMEC)⁺ and Cu(Arm)(PMEC) complexes {PMEC^2– = dianion of 1‐[2‐(phosphonomethoxy)ethyl]cytosine, Arm = 2, 2′‐bipyridine (Bpy) or 1, 10‐phenanthroline (Phen)} were measured by potentiometric pH titrations (aq. sol.; 25 °C; I = 0.1 M, NaNO₃) and compared with those of Cu(Arm)(H;PMEA)⁺ and Cu(Arm)(PMEA) {PMEA^2– = dianion of 9‐[2‐(phosphonomethoxy)ethyl]adenine},...

article

Erratum to “Lessons on the critical interplay between zinc binding and protein structure and dynamics” [JIB 121C (2013) 145–155]

Claudia A. Blindauer

Journal of Inorganic Biochemistry > 2013 > 123 > Complete > 88

article

Lessons on the critical interplay between zinc binding and protein structure and dynamics

Claudia A. Blindauer

Journal of Inorganic Biochemistry > 2013 > 121 > Complete > 145-155

Zinc is one of the most important micronutrients for virtually all living organisms, and hence, it is important to understand the molecular mechanisms for its homeostasis. Besides proteins involved in transmembrane transport, both extra- and intracellular zinc-binding proteins play important roles in the respective metabolic networks. Important examples for extracellular zinc transporters are mammalian...

article

Extent of Intramolecular π‐Stacks in Aqueous Solution in Mixed‐Ligand Copper(II) Complexes Formed by Heteroaromatic Amines and Several 2‐Aminopurine Derivatives of the Antivirally Active Nucleotide Analog 9‐[2‐(Phosphonomethoxy)ethyl]adenine (PMEA)

Raquel B. Gómez‐Coca, Claudia A. Blindauer, Astrid Sigel, Bert P. Operschall, more

Chemistry & Biodiversity > 9 > 9 > 2008 - 2034

The acidity constants of twofold protonated, antivirally active, acyclic nucleoside phosphonates (ANPs), H₂(PE)^±, where PE²⁻=9‐[2‐(phosphonomethoxy)ethyl]adenine (PMEA²⁻), 2‐amino‐9‐[2‐(phosphonomethoxy)ethyl]purine (PME2AP²⁻), 2,6‐diamino‐9‐[2‐(phosphonomethoxy)ethyl]purine (PMEDAP²⁻), or 2‐amino‐6‐(dimethylamino)‐9‐[2‐(phosphonomethoxy)ethyl]purine (PME(2A6DMAP)²⁻), as well as the stability constants...

article

Protein fractionation and detection for metalloproteomics: challenges and approaches

James P. Barnett, David J. Scanlan, Claudia A. Blindauer

Analytical and Bioanalytical Chemistry > 2012 > 402 > 10 > 3311-3322

At least one third of all proteins are thought to require a metal ion co-factor for their function. Recognition of the importance of metals in biological systems and major advances in analytical instrumentation and technology have led to the emergence of the new research area of metalloproteomics in recent years. Despite this progress, the experimental determination of in-vivo metal cofactors has...

article

Fractionation and identification of metalloproteins from a marine cyanobacterium

James P. Barnett, David J. Scanlan, Claudia A. Blindauer

Analytical and Bioanalytical Chemistry > 2012 > 402 > 10 > 3371-3377

Trace metals are essential for the growth of marine cyanobacteria, being required for key cellular processes such as photosynthesis and respiration. Despite this, the metalloproteomes of marine cyanobacteria are at present only poorly defined. In this study, we have probed the major cobalt, iron, manganese, and nickel-binding proteins in the marine cyanobacterium Synechococcus sp. WH8102 by using...

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The Tat protein export pathway and its role in cyanobacterial metalloprotein biosynthesis

James P. Barnett, Colin Robinson, David J. Scanlan, Claudia A. Blindauer

FEMS Microbiology Letters > 325 > 1 > 1 - 9

The Tat pathway is a common protein translocation system that is found in the bacterial cytoplasmic membrane, as well as in the cyanobacterial and plant thylakoid membranes. It is unusual in that the Tat pathway transports fully folded, often metal cofactor‐containing proteins across these membranes. In bacteria, the Tat pathway plays an important role in the biosynthesis of noncytoplasmic metalloproteins...

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Search results for: Claudia A. Blindauer

Fatty acids may influence insulin dynamics through modulation of albumin‐Zn²⁺ interactions

Metal Ion‐Coordinating Properties in Aqueous Solutions of the Antivirally Active Nucleotide Analogue (S)‐9‐[3‐Hydroxy‐2‐(phosphonomethoxy)propyl]adenine (HPMPA) – Quantification of Complex Isomeric Equilibria

Ischemia-modified albumin: Crosstalk between fatty acid and cobalt binding

Metal-ion binding properties of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir). A nucleotide analogue with activity against DNA viruses

Differential reactivity of closely related zinc(II)-binding metallothioneins from the plant Arabidopsis thaliana

Sediment Metal Contamination in the Kafue River of Zambia and Ecological Risk Assessment

O₂‐independent demethylation of trimethylamine N‐oxide by Tdm of Methylocella silvestris

Extent of intramolecular π stacks in aqueous solution in mixed-ligand copper(II) complexes formed by heteroaromatic amines and the anticancer and antivirally active 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG). A comparison with related acyclic nucleotide analogues

The reduced Co²⁺‐binding ability of ischaemia‐modified albumin is unlikely to be because of oxidative modification of the N‐terminus

Prion infection in cells is abolished by a mutated manganese transporter but shows no relation to zinc

Characterization of Folding Cores in the Cyclophilin A-Cyclosporin A Complex

A Canonical EF‐Loop Directs Ca²⁺‐Sensitivity in Phospholipase C‐η2

Allosteric modulation of zinc speciation by fatty acids

Extent of Intramolecular π Stacks in Aqueous Solution in Mixed‐Ligand Copper(II) Complexes Formed by Heteroaromatic Amines and 1‐[2‐(Phosphonomethoxy)ethyl]cytosine (PMEC), a Relative of Antivirally Active Acyclic Nucleotide Analogues (Part 72)^{[1, 2]}

Erratum to “Lessons on the critical interplay between zinc binding and protein structure and dynamics” [JIB 121C (2013) 145–155]

Lessons on the critical interplay between zinc binding and protein structure and dynamics

Extent of Intramolecular π‐Stacks in Aqueous Solution in Mixed‐Ligand Copper(II) Complexes Formed by Heteroaromatic Amines and Several 2‐Aminopurine Derivatives of the Antivirally Active Nucleotide Analog 9‐[2‐(Phosphonomethoxy)ethyl]adenine (PMEA)

Protein fractionation and detection for metalloproteomics: challenges and approaches

Fractionation and identification of metalloproteins from a marine cyanobacterium

The Tat protein export pathway and its role in cyanobacterial metalloprotein biosynthesis

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