Protein Interface Zinc Sites: The Role of Zinc in the Supramolecular Assembly of Proteins and in Transient Protein–Protein Interactions

Maret, Wolfgang

doi:10.1002/0470028637.met016

Cited by 13 publications

(9 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When cellular "free" zinc increases, zinc modulates, or may regulate, the biological functions of proteins with such sites. Candidates for zinc regulation are inhibitory zinc-binding sites on enzymes with nanomolar or lower affinity for zinc, such as protein tyrosine phosphatases and caspase-3 (14), or interfacial zinc sites, where zinc binding determines the quaternary or quinary structure of proteins (21). The results suggest regulatory roles of zinc ions at picomolar concentrations, a range that hitherto was inaccessible to biochemical exploration.…”

Section: Cellular Zinc Buffering Capacity and "Free" Zincmentioning

confidence: 97%

Cellular Zinc and Redox Buffering Capacity of Metallothionein/Thionein in Health and Disease

Maret

Krężel

2007

Mol Med

Self Cite

171

132

View full text Add to dashboard Cite

Zinc is involved in virtually all aspects of cellular and molecular biology as a catalytic, structural, and regulatory cofactor in over 1000 proteins. Zinc binding to proteins requires an adequate supply of zinc and intact molecular mechanisms for redistributing zinc ions to make them available at the right time and location. Several dozen gene products participate in this process, in which interactions between zinc and sulfur donors determine the mobility of zinc and establish coupling between cellular redox state and zinc availability. Specifically, the redox properties of metallothionein and its apoprotein thionein are critical for buffering zinc ions and for controlling fluctuations in the range of picomolar concentrations of "free" zinc ions in cellular signaling. Metallothionein and other proteins with sulfur coordination environments are sensitive to redox perturbations and can render cells susceptible to injury when oxidative stress compromises the cellular redox and zinc buffering capacity in chronic diseases. The implications of these fundamental principles for zinc metabolism in type 2 diabetes are briefly discussed.

show abstract

Section: Cellular Zinc Buffering Capacity and "Free" Zincmentioning

confidence: 97%

Cellular Zinc and Redox Buffering Capacity of Metallothionein/Thionein in Health and Disease

Maret

Krężel

2007

Mol Med

Self Cite

171

132

View full text Add to dashboard Cite

show abstract

“…The protein interface zinc binding site thus contains amino acid ligands that reside in the binding surface between two interacting proteins (or protein subunits), and where the ligands are supplied by both proteins (or protein subunits). The coordination properties are generally those of catalytic or structural zinc binding sites [42,43,53]. The general importance of zinc in biology, and the fact that zinc in living organisms mainly exists bound to proteins, make characterization of zinc in protein structure and function highly important.…”

Section: Metalloproteins and Zincmentioning

confidence: 99%

Medium- and short-chain dehydrogenase/reductase gene and protein families

Auld

Bergman

2008

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Zinc plays an important role in the structure and function of many enzymes, including alcohol dehydrogenases (ADHs) of the MDR type (mediumchain dehydrogenases/reductases). Active site zinc participates in catalytic events, and structural site zinc maintains structural stability. MDR-types of ADHs have both of these zinc sites but with some variation in ligands and spacing. The catalytic zinc sites involve three residues with different spacings from two separate protein segments, while the structural zinc sites involve four residues and cover a local segment of the protein chain (Cys97-Cys111 in horse liver class I ADH). This review summarizes properties of both ADH zinc sites, and relates them to zinc sites of proteins in general. In addition, it highlights a separate study of zinc binding peptide variants of the horse liver ADH structural zinc site. The results show that zinc coordination of the free peptide differs markedly from that of the enzyme (one His / three Cys versus four Cys), suggesting that the protein zinc site is in an energetically strained conformation relative to that of the peptide. This finding is a characteristic of an entatic state, implying a functional nature for this zinc site.

show abstract

“…Also, zinc ions bind transiently to proteins that are not recognized as zinc proteins. Such interactions include sites where zinc binds between protein subunits or inhibits protein functions, and sites that participate in cellular zinc re-distribution Auld 2001;Maret 2004b). Historically, research efforts focused mainly on the roles of catalytic and structural zinc ions in enzymes and other proteins.…”

Section: Introductionmentioning

confidence: 99%

Molecular aspects of human cellular zinc homeostasis: redox control of zinc potentials and zinc signals

2009

Self Cite

View full text Add to dashboard Cite

Zinc(II) ions are essential for all forms of life. In humans, they have catalytic and structural functions in an estimated 3,000 zinc proteins. In addition, they interact with proteins transiently when they regulate proteins or when proteins regulate cellular zinc re-distribution. As yet, these types of zinc proteins have been explored poorly. Therefore the number of zinc/protein interactions is potentially larger than that given by the above estimate. Confronted with such a wide range of functions, which affect virtually all aspects of cellular physiology, investigators have begun to elucidate the molecular mechanisms of cellular homeostatic control of zinc, especially the functions of transporter, sensor, and trafficking proteins, such as metallothioneins, in providing the correct amounts of zinc ions for the synthesis of zinc metalloproteins. The sulfur-containing amino acid cysteine in proteins has an important role in the cellular mobility of zinc ions. Sulfur-coordination environments provide sufficiently strong interactions with zinc ions; they can undergo fast ligand-exchange; and they can serve as molecular redox switches for zinc binding and release. For the cellular functions of zinc, the free zinc ion concentrations (zinc potentials, pZn = -log[Zn(2+)]) and the zinc buffering capacity are critically important parameters that need to be defined quantitatively. In the cytoplasm, free zinc ions are kept at picomolar concentrations as a minute fraction of the few hundred micromolar concentrations of total cellular zinc. However, zinc ion concentrations can fluctuate under various conditions. Zinc ions released intracellularly from the zinc/thiolate clusters of metallothioneins or secreted from specialized organelles are potent effectors of proteins and are considered zinc signals. The cellular zinc buffering capacity determines the threshold between physiological and pathophysiological actions of zinc ions. When drugs, toxins, other transition metal ions or reactive compounds compromise zinc buffering, large zinc ion fluctuations can injure cells through effects on redox biology and interactions of zinc ions with proteins that are normally not targeted.

show abstract

Protein Interface Zinc Sites: The Role of Zinc in the Supramolecular Assembly of Proteins and in Transient Protein–Protein Interactions

Cited by 13 publications

References 72 publications

Cellular Zinc and Redox Buffering Capacity of Metallothionein/Thionein in Health and Disease

Cellular Zinc and Redox Buffering Capacity of Metallothionein/Thionein in Health and Disease

Medium- and short-chain dehydrogenase/reductase gene and protein families

Molecular aspects of human cellular zinc homeostasis: redox control of zinc potentials and zinc signals

Contact Info

Product

Resources

About