Biological inorganic chemistry at the beginning of the 21st century

Gray, Harry B.

doi:10.1073/pnas.0730378100

Cited by 148 publications

(94 citation statements)

References 151 publications

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“…As a result, the concentrations of cellular metal ions have to be highly regulated in different parts of cells, as both deficiency and surplus of metal ions can disrupt normal functions (1)(2)(3)(4). To better understand the functions of metal ions in biology, it is important to detect metal ions selectively in living cells; such an endeavor will not only result in better understanding of cellular processes but also novel ways to reprogram these processes to achieve novel functions for biotechnological applications.…”

mentioning

confidence: 99%

In vitro selection of a sodium-specific DNAzyme and its application in intracellular sensing

Torabi¹,

Wu²,

McGhee³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

316

286

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Over the past two decades, enormous progress has been made in designing fluorescent sensors or probes for divalent metal ions. In contrast, the development of fluorescent sensors for monovalent metal ions, such as sodium (Na + ), has remained underdeveloped, even though Na + is one the most abundant metal ions in biological systems and plays a critical role in many biological processes. Here, we report the in vitro selection of the first (to our knowledge) Na + -specific, RNA-cleaving deoxyribozyme (DNAzyme) with a fast catalytic rate [observed rate constant (k obs ) ∼0.1 min −1 ], and the transformation of this DNAzyme into a fluorescent sensor for Na + by labeling the enzyme strand with a quencher at the 3′ end, and the DNA substrate strand with a fluorophore and a quencher at the 5′ and 3′ ends, respectively. The presence of Na + catalyzed cleavage of the substrate strand at an internal ribonucleotide adenosine (rA) site, resulting in release of the fluorophore from its quenchers and thus a significant increase in fluorescence signal. The sensor displays a remarkable selectivity (>10,000-fold) for Na + over competing metal ions and has a detection limit of 135 μM (3.1 ppm). Furthermore, we demonstrate that this DNAzyme-based sensor can readily enter cells with the aid of α-helical cationic polypeptides. Finally, by protecting the cleavage site of the Na + -specific DNAzyme with a photolabile o-nitrobenzyl group, we achieved controlled activation of the sensor after DNAzyme delivery into cells. Together, these results demonstrate that such a DNAzyme-based sensor provides a promising platform for detection and quantification of Na + in living cells.M etal ions play crucial roles in a variety of biochemical processes. As a result, the concentrations of cellular metal ions have to be highly regulated in different parts of cells, as both deficiency and surplus of metal ions can disrupt normal functions (1-4). To better understand the functions of metal ions in biology, it is important to detect metal ions selectively in living cells; such an endeavor will not only result in better understanding of cellular processes but also novel ways to reprogram these processes to achieve novel functions for biotechnological applications.Among the metal ions in cells, sodium (Na + ) serves particularly important functions, as changes in its concentrations influence the cellular processes of numerous living organisms and cells (5-8), such as epithelial and other excitable cells (9). As one of the most abundant metal ions in intracellular fluid (10), Na + affects cellular processes by triggering the activation of many signal transduction pathways, as well as influencing the actions of hormones (11). Therefore, it is important to carefully monitor the concentrations of Na + in cells. Toward this goal, instrumental analyses by atomic absorption spectroscopy (12), Xray fluorescence microscopy (13), and 23 Na NMR (14) have been used to detect the concentration of intracellular Na + . However, it is difficult to use these methods to o...

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mentioning

confidence: 99%

In vitro selection of a sodium-specific DNAzyme and its application in intracellular sensing

Torabi¹,

Wu²,

McGhee³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

316

286

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“…R ational design of proteins that mimic both structure and function of more complex native enzymes has been a long soughtafter goal, as the process is an ultimate test of our knowledge and an excellent means to develop advanced biocatalysts (1)(2)(3). Although designed proteins that model the structure of native enzymes have been known for a while (4)(5)(6)(7)(8)(9)(10), successful designs of proteins that mimic both the structure and function of native enzymes have been reported only recently (11)(12)(13)(14)(15)(16).…”

mentioning

confidence: 99%

Roles of glutamates and metal ions in a rationally designed nitric oxide reductase based on myoglobin

Lin

Yeung²,

Gao³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

108

140

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A structural and functional model of bacterial nitric oxide reductase (NOR) has been designed by introducing two glutamates (Glu) and three histidines (His) in sperm whale myoglobin. X-ray structural data indicate that the three His and one Glu (V68E) residues bind iron, mimicking the putative Fe B site in NOR, while the second Glu (I107E) interacts with a water molecule and forms a hydrogen bonding network in the designed protein. Unlike the first Glu (V68E), which lowered the heme reduction potential by ∼110 mV, the second Glu has little effect on the heme potential, suggesting that the negatively charged Glu has a different role in redox tuning. More importantly, introducing the second Glu resulted in a ∼100% increase in NOR activity, suggesting the importance of a hydrogen bonding network in facilitating proton delivery during NOR reactivity. In addition, EPR and X-ray structural studies indicate that the designed protein binds iron, copper, or zinc in the Fe B site, each with different effects on the structures and NOR activities, suggesting that both redox activity and an intermediate five-coordinate heme-NO species are important for high NOR activity. The designed protein offers an excellent model for NOR and demonstrates the power of using designed proteins as a simpler and more welldefined system to address important chemical and biological issues.biomimetic models | heme-copper oxidase | metalloprotein | protein design | protein engineering R ational design of proteins that mimic both structure and function of more complex native enzymes has been a long soughtafter goal, as the process is an ultimate test of our knowledge and an excellent means to develop advanced biocatalysts (1-3). Although designed proteins that model the structure of native enzymes have been known for a while (4-10), successful designs of proteins that mimic both the structure and function of native enzymes have been reported only recently (11-16). While being able to design such functional proteins is laudable, the impact of such an achievement would be greater if the designed proteins can be used to address fundamental issues in chemistry and biology that are difficult to tackle by other methods. One primary example is the roles of conserved glutamates and metal ions in bacterial nitric oxide reductase (NOR) (17)(18)(19).NO is critical for all life (20). Bacterial denitrification is a crucial part of the nitrogen cycle in nature that involves a four-step, five-electron reduction of nitrate (NO 3 − ) to dinitrogen (N 2 ) (17, 19). Bacterial NOR is a membrane-bound protein that catalyzes one step of this process, namely, the two-electron reduction of NO to N 2 O (17, 19). With no crystal or solution structure available for bacterial NOR to date, sequence alignments and homology modeling (21, 22) have indicated that NOR is structurally homologous to the largest subunit (subunit I) of hemecopper oxidases (HCOs) (23), enzymes that catalyze reduction of O 2 to water. The active sites of both NOR and HCO contain a proximal histidine-coo...

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“…In addition, the organic-containing spintronic devices present potentially lower processing costs compared to inorganic materials due to the use of changing and optimizing solvents, pH, ionic strength and other variables that are much easier and common to manipulate that those required in inorganic chemistry. A common strategy to induce magnetic order and switching in metalloporphyrin systems is the deposition of the molecules onto a ferromagnetic metal surface leading to the parallel alignment of spin of the central ion with the substrate magnetization [10][11][12]. However, other types of interactions that are able to promote magnetization switching in porphyrin systems remain to be investigated.…”

Section: Introductionmentioning

confidence: 99%

“…Metalloporphyrins are very versatile molecules that were selected by nature to act in a variety of biological functions, such as electron transfer, light harvesting antennas, biocatalysis, molecular oxygen transport, cell signaling, and even cell death [1][2][3][4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Interaction of Fe3+meso-tetrakis (2,6-dichloro-3-sulfonatophenyl) porphyrin with cationic bilayers: magnetic switching of the porphyrin and magnetic induction at the interface

et al. 2011

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Biological inorganic chemistry at the beginning of the 21st century

Cited by 148 publications

References 151 publications

In vitro selection of a sodium-specific DNAzyme and its application in intracellular sensing

In vitro selection of a sodium-specific DNAzyme and its application in intracellular sensing

Roles of glutamates and metal ions in a rationally designed nitric oxide reductase based on myoglobin

Interaction of Fe3+meso-tetrakis (2,6-dichloro-3-sulfonatophenyl) porphyrin with cationic bilayers: magnetic switching of the porphyrin and magnetic induction at the interface

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