Histidine tracts in human transcription factors: insight into metal ion coordination ability

AbstractHematopoiesis requires finely tuned regulation of gene expression at each stage of development. The regulation of gene transcription involves not only individual transcription factors (TFs) but also transcription complexes (TCs) composed of transcription factor(s) and multisubunit cofactors. In their normal compositions, TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis. The integration of posttranslational and conformational modifications in the chromatin landscape, nucleosomes, histones and interacting components via the cofactor–TF interplay is critical to optimal TF activity. Mutations or translocations of cofactor genes are expected to alter cofactor–TF interactions, which may be causative for the pathogenesis of various hematologic disorders. Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy. In this review, we summarize the current knowledge regarding the models and functions of cofactor–TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies. This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.

Download Full-text

Metal Ion Mediated Cellulose Nanofibrils Transient Network in Covalently Cross-linked Hydrogels: Mechanistic Insight into Morphology and Dynamics

Biomacromolecules ◽

10.1021/acs.biomac.6b01915 ◽

2017 ◽

Vol 18 (3) ◽

pp. 1019-1028 ◽

Cited By ~ 43

Author(s):

Jun Yang ◽

Feng Xu ◽

Chun-Rui Han

Keyword(s):

Metal Ion ◽

Cellulose Nanofibrils ◽

Mechanistic Insight ◽

Transient Network ◽

Insight Into

Download Full-text

Comparative Thermochemistry of Metalloporphyrin Isomers as a Function of Metal Ion Size. A Possible Insight into Nature's Choice of Porphyrin over Isomeric Ligands

Inorganic Chemistry ◽

10.1021/ic9807994 ◽

1998 ◽

Vol 37 (24) ◽

pp. 6276-6280 ◽

Cited By ~ 6

Author(s):

Abhik Ghosh ◽

Torgil Vangberg

Keyword(s):

Metal Ion ◽

Ion Size ◽

Insight Into

Download Full-text

Fluorescent signaling provides deeper insight into aromatic anion uptake by metal-ion activated molecular receptors

New Journal of Chemistry ◽

10.1039/b719183a ◽

2008 ◽

Vol 32 (9) ◽

pp. 1500 ◽

Cited By ~ 14

Author(s):

Adam J. Bradbury ◽

Stephen F. Lincoln ◽

Kevin P. Wainwright

Keyword(s):

Metal Ion ◽

Molecular Receptors ◽

Insight Into ◽

Anion Uptake

Download Full-text

MetLigDB: a web-based database for the identification of chemical groups to design metalloprotein inhibitors

Journal of Applied Crystallography ◽

10.1107/s0021889811022503 ◽

2011 ◽

Vol 44 (4) ◽

pp. 878-881 ◽

Cited By ~ 8

Author(s):

Hwanho Choi ◽

Hongsuk Kang ◽

Hwangseo Park

Keyword(s):

Drug Discovery ◽

Metal Ions ◽

Metal Ion ◽

Central Metal ◽

Amino Acid Residues ◽

Web Based ◽

Additional Information ◽

Chemical Groups ◽

Insight Into ◽

Chelating Groups

MetLigDB (http://silver.sejong.ac.kr/MetLigDB) is a publicly accessible web-based database through which the interactions between a variety of chelating groups and various central metal ions in the active site of metalloproteins can be explored in detail. Additional information can also be retrieved, including protein and inhibitor names, the amino acid residues coordinated to the central metal ion, and the binding affinity of the inhibitor for the target metalloprotein. Although many metalloproteins have been considered promising targets for drug discovery, it is difficult to discover new inhibitors because of the difficulty in designing a suitable chelating moiety to impair the catalytic activity of the central metal ion. Because both common and specific chelating groups can be identified for varying metal ions and the associated coordination environments, MetLigDB is expected to give users insight into designing new inhibitors of metalloproteins for drug discovery.

Download Full-text

Immobilized metal-ion affinity systems for recovery and structure–function studies of proteins at molecular, supramolecular, and cellular levels

Pure and Applied Chemistry ◽

10.1351/pac-con-09-01-18 ◽

2010 ◽

Vol 82 (1) ◽

pp. 39-55 ◽

Cited By ~ 8

Author(s):

Rajasekar R. Prasanna ◽

Mookambeswaran A. Vijayalakshmi

Keyword(s):

Capillary Electrophoresis ◽

Recombinant Proteins ◽

Gel Electrophoresis ◽

Metal Ion ◽

Immobilized Metal Affinity Chromatography ◽

Metal Affinity ◽

Purification Technique ◽

Affinity Gel Electrophoresis ◽

Insight Into ◽

Histidine Tag

Immobilized metal-ion affinity (IMA) adsorption is a collective term that is used to include all kinds of adsorptions where the metal ion serves as the characteristic and most essential part of adsorption center. Of all the IMA techniques, immobilized metal-affinity chromatography (IMAC) has been gaining popularity as the choice of purification technique for proteins. IMAC represents a separation technique that is primarily useful for proteins with natural surface exposed-histidine residues and for recombinant proteins with engineered histidine tag. This review also gives insight into other nonchromatographic applications of IMA adsorption such as immobilized metal-ion affinity gel electrophoresis (IMAGE), immobilized metal-ion affinity capillary electrophoresis (IMACE), and immobilized metal-ion affinity partitioning (IMAP).

Download Full-text

Metal ion – biomolecule interactions. X. Synthesis, spectroscopic and magnetic resonance investigations of methylmercury(II) complexes of the sulfur modified nucleosides 6- mercaptopurine riboside and 2-amino-6-mercaptopurine riboside

Canadian Journal of Chemistry ◽

10.1139/v86-069 ◽

1986 ◽

Vol 64 (3) ◽

pp. 442-448 ◽

Cited By ~ 15

Author(s):

E. Buncel ◽

R. Kumar ◽

A. R. Norris

Keyword(s):

Aqueous Solution ◽

Metal Ion ◽

Chemotherapeutic Agents ◽

Modified Nucleosides ◽

Coupling Constants ◽

Heterocyclic Ligands ◽

Methylmercury Poisoning ◽

Insight Into ◽

C Nmr ◽

Ligand Bond

A number of methylmercurated complexes of 6-mercaptopurine riboside and 2-amino-6-mercaptopurine riboside (6-MNucH2) containing S-bound CH3Hg(II) in neutral and cationic complexes (as in [CH3Hg(6-MNucH)] and [CH3Hg(6-MNucH2)]NO3), S- and N-bound CH3Hg(II) (as in [(CH3Hg)2(6-MNucH)]NO3), and S-, N-, C-bound CH3Hg(II) (as in [(CH3Hg)3(6-MNuc)]NO3) have been prepared in aqueous solution at appropriate pH and mole ratios of the constituents. The complexes were characterized by means of 1H and 13C nmr and ir spectroscopy and elemental analysis. Formation of C-bound methylmercurated species extends our previous results obtained with xanthosine, inosine, and imidazole derivatives, and substantiates our proposal that activation through electrophilic coordination at N(7) is a requirement for C(8)—H abstraction. 2J(1H–199Hg) coupling constants, measured in (CD3)2SO for a number of CH3Hg(II) complexes of N-, S-, and C-donor heterocyclic ligands, including the 6-mercaptopurine riboside of the present study, correlate well with the 1J(13C–199Hg) coupling constants, according to 1J = 8.4602J − 155.6. The significance of this correlation in terms of the strength of the Hg–ligand bond is considered. The results could provide insight into the apparent selectivity of binding of CH3Hg(II) by bio-ligands, as well as in the design of chemotherapeutic agents for the treatment of methylmercury poisoning.

Download Full-text

Integrating naive Bayes models and external knowledge to examine copper and iron homeostasis in S. cerevisiae

Physiological Genomics ◽

10.1152/physiolgenomics.2000.4.2.127 ◽

2000 ◽

Vol 4 (2) ◽

pp. 127-135 ◽

Cited By ~ 24

Author(s):

E. J. Moler ◽

D. C. Radisky ◽

I. S. Mian

Keyword(s):

Cell Cycle ◽

Transcription Factors ◽

Metal Ion ◽

Iron Homeostasis ◽

Graphical Model ◽

Naive Bayes ◽

Naïve Bayes ◽

Diauxic Shift ◽

Ion Regulation ◽

External Knowledge

A novel suite of analytical techniques and visualization tools are applied to 78 published transcription profiling experiments monitoring 5,687 Saccharomyces cerevisiae genes in studies examining cell cycle, responses to stress, and diauxic shift. A naive Bayes model discovered and characterized 45 classes of gene profile vectors. An enrichment measure quantified the association between these classes and specific external knowledge defined by four sets of categories to which genes can be assigned: 106 protein functions, 5 stages of the cell cycle, 265 transcription factors, and 16 chromosomal locations. Many of the 38 genes in class 42 are known to play roles in copper and iron homeostasis. The 17 uncharacterized open reading frames in this class may be involved in similar homeostatic processes; human homologs of two of them could be associated with as yet undefined disease states arising from aberrant metal ion regulation. The Met4, Met31, and Met32 transcription factors may play a role in coregulating genes involved in copper and iron metabolism. Extensions of the simple graphical model used for clustering to learning more complex models of genetic networks are discussed.

Download Full-text