Interprotein metal ion exchange between cadmium-carbonic anhydrase and apo- or zinc-metallothionein

Ejnik, John W.; Muñoz, Amalia; Gan, Tong J.; Shaw, C. Frank; Petering, David H.

doi:10.1007/s007750050351

Cited by 44 publications

(40 citation statements)

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“…Little is known about the rates of reaction of Cd-protein complexes with apoMT. The present results as well as those showing that Cd 2 -Tramtrack and Cd-carbonic anhydrase are reactive with apoMT provide a chemical underpinning for the hypothesis that MT is protective against Cd 2+ [28,31]. …”

Section: Discussionsupporting

confidence: 67%

“…The location of the key thiolates at the Cterminus of the MT peptide would minimize the steric barrier of reaction between two macro-molecules, apo-MT and another metal-containing protein, and, thereby, facilitate the bimolecular interaction between them. In support of this proposal, a peptide with the amino acid sequence of 49-61 is much more reactive with Cd-carbonic anhydrase than is apoMT [31].…”

Section: Discussionmentioning

confidence: 79%

“…Considering these factors, the difference in rate constant for the two reactions was surprisingly small. In another study it was shown that apoMT was actually a much more effective competing ligand than EDTA for Cd 2+ bound to carbonic anhydrase [31]. The two results underscore that apoMT is a kinetically competent metal-binding ligand even when Zn 2+ or Cd 2+ are bound to other structures that present large steric obstructions.…”

Section: Discussionmentioning

confidence: 94%

“…However, little is known about the sites, such as metalloproteins, to which Cd 2+ binds and the properties of the reactions of apo-or Zn-MT with such sites. Studies of the reaction of apoMT and one of its component peptide sequences with Cd-carbonic anhydrase showed that both were remarkably effective in competing for protein-bound Cd 2+ [31,32]. There is evidence that, in vitro, Cd 2+ can substitute for Zn 2+ in zinc-finger structures and that such substitution can change the activities of the finger domains [22,28,33].…”

Section: Introductionmentioning

confidence: 99%

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Interprotein metal exchange between transcription factor IIIa and apo-metallothionein

Huang

Shaw

Petering

2004

Journal of Inorganic Biochemistry

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Zn 2+ and Cd 2+ ion exchange between transcription factor IIIA (TFIIIA) and apo-metallothionein (MT) were studied using a combination of methods including chromatography, ultrafiltration and UV spectroscopy. Under near stoichiometric conditions, apoMT was able to remove most if not all of the zinc ions from TFIIIA, whether or not the TFIIIA was bound to the 5S DNA internal control region (ICR), and concomitantly inhibit its DNA-binding activity as indicated by an electrophoretic mobility shift assay. The kinetics of the two processes were similar. The rate of the metal exchange reaction increased with the concentrations of both reactants. A second-order rate constant of 30 ± 10 M −1 s −1 was calculated. Similar observations were made for the reaction between apoMT and Cd-substituted TFIIIA, which proceeded without observable intermediates according to a spectrophotometric analysis. A very slow metal ion exchange occurred between Cd-TFIIIA and Zn-MT, but not between Cd-MT and Zn-TFIIIA. Comparative studies on the reaction of TFIIIA with a small competing ligand, ethylenedinitrilo-tetraacetic acid (EDTA), were also conducted. Although EDTA reacts with free Zn-TFIIIA, under similar conditions it failed to compete for Zn 2+ bound as Zn-TFIIIA-ICR.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Interprotein metal exchange between transcription factor IIIa and apo-metallothionein

Huang

Shaw

Petering

2004

Journal of Inorganic Biochemistry

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“…A possibly direct interaction between the metallothionein/thionein couple and structural zinc binding domains in other proteins has been discussed for the two-zinc finger protein Tamtrack (15) and a direct transfer of zinc via discrete (ternary) intermediates has been postulated from theoretical considerations (16). Interprotein metal ion exchange between cadmium-substituted carbonic anhydrase and apo-or zinc-metallothionein on a time scale of seconds to minutes has been demonstrated (17). A direct transfer of zinc ions requires formation of intermediary ternary complexes with a sufficient lifetime to allow the subsequent ligand exchange reaction to occur.…”

mentioning

confidence: 99%

On the Competition for Available Zinc

Heinz¹,

Kiefer

Tholey

et al. 2005

Journal of Biological Chemistry

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Extended x-ray absorption fine structure (EXAFS) spectroscopy was combined with thermodynamic and kinetic approaches to investigate zinc binding to a zinc finger (C 2 H 2 ) and a tetrathiolate (C 4 ) peptide. Both peptides represent structural zinc sites of proteins and rapidly bind a single zinc ion with picomolar dissociation constants. In competition with EDTA the transfer of peptide-bound zinc ions proved to be 6 orders of magnitude faster than predicted for a dissociation-association mechanism thus requiring ligand exchange mechanisms via peptide-zinc-EDTA complexes. EXAFS spectra of C 2 H 2 showed the expected Cys 2 His 2 -ligand geometry when fully loaded with zinc. For a 2-fold excess of peptide, however, the existence of zinc-bridged peptidepeptide complexes with dominating sulfur coordination could be clearly shown. Whereas zinc binding kinetics of C 2 H 2 appeared as a simple second order process, the suggested mechanism for C 4 comprises a zinc-bridged Zn-(C 4 ) 2 species as well as a Zn-C 4 species with less than 4 metal-bound thiolates, which is supported by EXAFS results. A rapid equilibrium of bound and unbound states of individual ligands might explain the kinetic instability of zinc-peptide complexes, which enables fast ligand exchange during the encounter of occupied and unoccupied acceptor sites. Depending on relative concentrations and stabilities, this results in a rapid transfer of zinc ions in the virtual absence of free zinc ions, as seen for the zinc transfer to EDTA, or in the formation of zinc-bridged complexes, as seen for both peptides with excess of peptides over available zinc.Within the last decade the generally accepted roles of protein-bound zinc in catalysis and structure stabilization were complemented by regulatory functions. Protein binding sites have been classified as "catalytic," "co-catalytic," and "structural" zinc sites (1). A fourth type, namely "interface" was added recently (2). The possible role of a variable zinc occupancy of protein sites as a modification that provides a pathway for intracellular information transfer has been discussed (3), and the steadily growing number of known zinc proteins involved in gene regulation led to the suggestion that some classes of proteins might transduce changes in available zinc levels into changes in patterns of gene expression (4). An update of recent findings in zinc biology (5) now supports the view of zinc as a key element in cellular regulation.An important question with respect to a regulatory function, however, concerns the controversially discussed concentration of free zinc ions in different physiological environments. Cells react on a changed zinc supply by e.g. an activated transcription of metallothionein (Ref. 6 and references therein) or changes in the activity of zinc-sensing transcription activators like Zap1 (7) and MTF-1 (8). In the latter cases zinc binding to individual zinc finger motifs is supposed to induce structural changes, which in turn modify the functionality of the proteins. If the transduction ...

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Zinc Proteomics

Nowakowski

Karim

Petering

2015

Encyclopedia of Inorganic and Bioinorganic Chemistry

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The formation of the Zn‐proteome involves a complex array of interactions of Zn 2+ with cellular proteins, beginning with transporters that govern the movement of Zn 2+ into and from the cytosol and organelles. Within these compartments, free Zn 2+ concentration is maintained at nanomolar to picomolar levels through extensive buffering by components of the proteome such as metallothionein. Current information favors the buffer as the source of Zn 2+ for the constitution of native Zn‐proteins; but neither equilibrium nor kinetic results demonstrate clearly how trafficking of Zn 2+ to specific sites occurs. The chemical basis of Zn 2+ ‐based signaling, illustrated with the transcription factor MTF‐1, is similarly ambiguous. Once formed, the Zn‐proteome is preserved under Zn 2+ ‐deficient conditions, but is susceptible to widespread metal exchange with Cd 2+ and reaction with other xenobiotics. Zn‐proteomic research extensively utilizes fluorescent sensors for Zn 2+ . Two of these, TSQ and Zinquin, form adducts with significant fractions of the Zn‐proteome and thereby reveal their status and reactivity under a variety of physiological and pathological conditions. The next step in the evolution of zinc proteomics will be to deconvolute collective Zn‐proteomic behavior into the reactions of individual Zn‐proteins. Methods are discussed that support this advance.

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Interprotein metal ion exchange between cadmium-carbonic anhydrase and apo- or zinc-metallothionein

Cited by 44 publications

References 0 publications

Interprotein metal exchange between transcription factor IIIa and apo-metallothionein

Interprotein metal exchange between transcription factor IIIa and apo-metallothionein

On the Competition for Available Zinc

Zinc Proteomics

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