?XANES: In vivo imaging of metal-protein coordination environments.
Ontology highlight
ABSTRACT:
SUBMITTER: James SA
PROVIDER: S-EPMC4748213 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The presence of metal centers with often highly conserved coordination environments is crucial for roughly half of all proteins, having structural, regulatory, or enzymatic function. To understand and mimic the function of metallo-enzymes, bioinorganic chemists pursue the challenge of synthesizing model compounds with well-defined, often heteroleptic metal sites. Recently, we reported the design of tailored homoleptic coordination environments for various transition metal cations based on unimolecular DNA G-quadruplex structures, templating the regioselective positioning of imidazole ligandosides L I . Here, we expand this modular system to more complex, heteroleptic coordination environments by combining L I with a new benzoate ligandoside L B within the same oligonucleotide. The modifications still allow the correct folding of parallel tetramolecular and antiparallel unimolecular G-quadruplexes. Interestingly, the incorporation of L B results in strong destabilization expressed in lower thermal denaturation temperatures T m . While no transition metal cations could be bound by G-quadruplexes containing only L B , heteroleptic derivatives containing both L I and L B were found to complex CuII, NiII, and ZnII. Especially in case of CuII we found strong stabilizations of up to ΔT m = +34°C. The here shown system represents an important step toward the design of more complex coordination environments inside DNA scaffolds, promising to culminate in the preparation of functional metallo-DNAzymes.
| S-EPMC7000376 | biostudies-literature
Project description:Two types of imidazole ligands were introduced both at the end of tetramolecular and into the loop region of unimolecular DNA G-quadruplexes. The modified oligonucleotides were shown to complex a range of different transition-metal cations including NiII , CuII , ZnII and CoII , as indicated by UV/Vis absorption spectroscopy and ion mobility mass spectrometry. Molecular dynamics simulations were performed to obtain structural insight into the investigated systems. Variation of ligand number and position in the loop region of unimolecular sequences derived from the human telomer region (htel) allows for a controlled design of distinct coordination environments with fine-tuned metal affinities. It is shown that CuII , which is typically square-planar coordinated, has a higher affinity for systems offering four ligands, whereas NiII prefers G-quadruplexes with six ligands. Likewise, the positioning of ligands in a square-planar versus tetrahedral fashion affects binding affinities of CuII and ZnII cations, respectively. Gaining control over ligand arrangement patterns will spur the rational development of transition-metal-modified DNAzymes. Furthermore, this method is suited to combine different types of ligands, for example, those typically found in metalloenzymes, inside a single DNA architecture.
| S-EPMC6899475 | biostudies-literature
Project description:The one-step self-assembly preparation of multifunctional gadolinium (Gd)-ytterbium (Yb) mixed-metal nanoscale coordination polymers (NCPs) with Ru[4,4'-(COOH)2bpy]32+ (LRu , bpy = bipyridyl) as a ligand is reported. The Gd/Yb ratio in the NCPs is easily tuned by their ratio in the precursors while the self-limiting growth is realized with the high coordination valence and rigid steric structure of the precursors. The inherent properties of the precursors, including the magnetic resonance (MR) response of Gd3+, the X-ray attenuation properties of Yb3+, and the red fluorescence and the singlet-oxygen generation of LRu , are well retained in the mixed-metal NCPs. In vivo fluorescence-MR-X-ray computed tomography (CT), triple-modality imaging and photodynamic therapy (PDT) are achieved using the mixed-metal NCPs as a probe. The triple-modality imaging integrates the high sensitivity of red fluorescence imaging, the deep penetration of MR imaging, and the 3D spatial resolution of CT imaging, thus providing comprehensive and complementary imaging information and facilitating the efficient imaging-guided PDT. For the first time, triple-modality imaging and a PDT agent were prepared with an easy and robust procedure, a tunable mixed-metal ratio, a high yield, and endogenous signal units.
| S-EPMC5465558 | biostudies-literature
Project description:Analysis of metal-protein interaction distances, coordination numbers, B-factors (displacement parameters), and occupancies of metal-binding sites in protein structures determined by X-ray crystallography and deposited in the PDB shows many unusual values and unexpected correlations. By measuring the frequency of each amino acid in metal ion-binding sites, the positive or negative preferences of each residue for each type of cation were identified. Our approach may be used for fast identification of metal-binding structural motifs that cannot be identified on the basis of sequence similarity alone. The analysis compares data derived separately from high and medium-resolution structures from the PDB with those from very high-resolution small-molecule structures in the Cambridge Structural Database (CSD). For high-resolution protein structures, the distribution of metal-protein or metal-water interaction distances agrees quite well with data from CSD, but the distribution is unrealistically wide for medium (2.0-2.5A) resolution data. Our analysis of cation B-factors versus average B-factors of atoms in the cation environment reveals substantial numbers of structures contain either an incorrect metal ion assignment or an unusual coordination pattern. Correlation between data resolution and completeness of the metal coordination spheres is also found.
| S-EPMC2872550 | biostudies-literature
Project description: Not available
| S-EPMC4832915 | biostudies-literature
Project description:In correlated systems, intermediate states usually appear transiently across phase transitions even at the femtosecond scale. It therefore remains an open question how to determine these intermediate states-a critical issue for understanding the origin of their correlated behaviour. Here we report a surface coordination route to successfully stabilize and directly image an intermediate state in the metal-insulator transition of vanadium dioxide. As a prototype metal-insulator transition material, we capture an unusual metal-like monoclinic phase at room temperature that has long been predicted. Coordinate bonding of L-ascorbic acid molecules with vanadium dioxide nanobeams induces charge-carrier density reorganization and stabilizes metallic monoclinic vanadium dioxide, unravelling orbital-selective Mott correlation for gap opening of the vanadium dioxide metal-insulator transition. Our study contributes to completing phase-evolution pathways in the metal-insulator transition process, and we anticipate that coordination chemistry may be a powerful tool for engineering properties of low-dimensional correlated solids.
| S-EPMC5474733 | biostudies-literature
Project description:Members of the ArsR/SmtB family of transcriptional repressors, such as CadC, regulate the intracellular levels of heavy metals like Cd(II), Hg(II), and Pb(II). These metal sensing proteins bind their target metals with high specificity and affinity, however, a lack of structural information about these proteins makes defining the coordination sphere of the target metal difficult. Lingering questions as to the identity of Cd(II) coordination in CadC are addressed via protein design techniques. Two designed peptides with tetrathiolate metal binding sites were prepared and characterized, revealing fast exchange between CdS3O and CdS4 coordination spheres. Correlation of (111m)Cd PAC spectroscopy and (113)Cd NMR spectroscopy suggests that Cd(II) coordinated to CadC is in fast exchange between CdS3O and CdS4 forms, which may provide a mechanism for rapid sensing of heavy metal contaminants by this regulatory protein.
| S-EPMC5250511 | biostudies-literature
Project description:Porous metal-organic frameworks (MOFs) have shown wide applications in catalysis, gas storage and separation due to their highly tunable porosity, connectivity and local structures. However, the electron-beam sensitivity of MOFs makes it difficult to achieve the atomic imaging of their bulk and local structures under (scanning) transmission electron microscopy ((S)TEM) to study their structure-property relations. Here, we report the low-dose imaging of a beam-sensitive MOF, MIL-101, under a Cs-corrected STEM based on the integrated differential phase contrast (iDPC) technique. The images resolve the coordination of Cr nodes and organic linkers inside the frameworks with an information transfer of ~1.8Å. The local structures in MIL-101 are also revealed under iDPC-STEM, including the surfaces, interfaces and defects. These results provide an extensible method to image various beam-sensitive materials with ultrahigh resolution, and unravel the whole framework architectures for further defect and surface engineering of MOFs towards tailored functions.
| S-EPMC7264187 | biostudies-literature
Project description:Beetle luciferases have been adapted for live cell imaging where bioluminescence is dependent on the cellular availability of ATP, O2, and added luciferin. Previous Photinus pyralis red-emitting variants with high Km values for ATP have performed disappointingly in live cells despite having much higher relative specific activities than enzymes like Click Beetle Red (CBR). We engineered a luciferase variant PLR3 having a Km value for ATP similar to CBR and ?2.6-fold higher specific activity. The red-emitting PLR3 was ?2.5-fold brighter than CBR in living HEK293T and HeLa cells, an improvement consistent with the importance of the Km value in low ATP environments.
| S-EPMC5730985 | biostudies-literature
Project description:To mimic a hypothetical pathway for protein evolution, we previously tailored a monomeric protein (cyt cb562 ) for metal-mediated self-assembly, followed by re-design of the resulting oligomers for enhanced stability and metal-based functions. We show that a single hydrophobic mutation on the cyt cb562 surface drastically alters the outcome of metal-directed oligomerization to yield a new trimeric architecture, (TriCyt1)3. This nascent trimer was redesigned into second and third-generation variants (TriCyt2)3 and (TriCyt3)3 with increased structural stability and preorganization for metal coordination. The three TriCyt variants combined furnish a unique platform to 1) provide tunable coupling between protein quaternary structure and metal coordination, 2) enable the construction of metal/pH-switchable protein oligomerization motifs, and 3) generate a robust metal coordination site that can coordinate all mid-to-late first-row transition-metal ions with high affinity.
| S-EPMC7983065 | biostudies-literature