scholarly journals The Role of Zinc in Copper Homeostasis of Aspergillus fumigatus

2020 ◽  
Vol 21 (20) ◽  
pp. 7665
Author(s):  
Suzie Kang ◽  
Hyewon Seo ◽  
Hee-Soo Moon ◽  
Joon-Ho Kwon ◽  
Yong-Sung Park ◽  
...  
Keyword(s):  
Metal Ion ◽  
Zinc Concentration ◽  
Copper Metabolism ◽  
Copper Homeostasis ◽  
Binding Activity ◽  
Upstream Region ◽  
Growth Defect ◽  
Binding Motif ◽  
Copper Supplementation ◽  
Living Organisms

Copper is an essential metal ion that performs many physiological functions in living organisms. Deletion of Afmac1, which is a copper-responsive transcriptional activator in A. fumigatus, results in a growth defect on aspergillus minimal medium (AMM). Interestingly, we found that zinc starvation suppressed the growth defect of the Δafmac1 strain on AMM. In addition, the growth defect of the Δafmac1 strain was recovered by copper supplementation or introduction of the CtrC gene into the Δafmac1 strain. However, chelation of copper by addition of BCS to AMM failed to recover the growth defect of the Δafmac1 strain. Through Northern blot analysis, we found that zinc starvation upregulated CtrC and CtrA2, which encode membrane copper transporters. Interestingly, we found that the conserved ZafA binding motif 5′-CAA(G)GGT-3′ was present in the upstream region of CtrC and CtrA2 and that mutation of the binding motif led to failure of ZafA binding to the upstream region of CtrC and upregulation of CtrC expression under zinc starvation. Furthermore, the binding activity of ZafA to the upstream region of CtrC was inversely proportional to the zinc concentration, and copper inhibited the binding of ZafA to the upstream region of CtrC under a low zinc concentration. Taken together, these results suggest that ZafA upregulates copper metabolism by binding to the ZafA binding motif in the CtrC promoter region under low zinc concentration, thus regulating copper homeostasis. Furthermore, we found that copper and zinc interact in cells to maintain metal homeostasis.

scholarly journals The Role of Zinc in Gliotoxin Biosynthesis of Aspergillus fumigatus

2019 ◽  
Vol 20 (24) ◽  
pp. 6192 ◽  
Author(s):  
Hyewon Seo ◽  
Suzie Kang ◽  
Yong-Sung Park ◽  
Cheol-Won Yun
Keyword(s):  
Aspergillus Fumigatus ◽  
Microarray Analysis ◽  
Binding Activity ◽  
Upstream Region ◽  
Human Macrophage ◽  
Transcription Activator ◽  
Binding Motifs ◽  
Host Defense System ◽  
Living Organisms

Zinc performs diverse physiological functions, and virtually all living organisms require zinc as an essential trace element. To identify the detailed function of zinc in fungal pathogenicity, we carried out cDNA microarray analysis using the model system of Aspergillus fumigatus, a fungal pathogen. From microarray analysis, we found that the genes involved in gliotoxin biosynthesis were upregulated when zinc was depleted, and the microarray data were confirmed by northern blot analysis. In particular, zinc deficiency upregulated the expression of GliZ, which encodes a Zn2-Cys6 binuclear transcription factor that regulates the expression of the genes required for gliotoxin biosynthesis. The production of gliotoxin was decreased in a manner inversely proportional to the zinc concentration, and the same result was investigated in the absence of ZafA, which is a zinc-dependent transcription activator. Interestingly, we found two conserved ZafA-binding motifs, 5′-CAAGGT-3′, in the upstream region of GliZ on the genome and discovered that deletion of the ZafA-binding motifs resulted in loss of ZafA-binding activity; gliotoxin production was decreased dramatically, as demonstrated with a GliZ deletion mutant. Furthermore, mutation of the ZafA-binding motifs resulted in an increase in the conidial killing activity of human macrophage and neutrophil cells, and virulence was decreased in a murine model. Finally, transcriptomic analysis revealed that the expression of ZafA and GliZ was upregulated during phagocytosis by macrophages. Taken together, these results suggest that zinc plays an important role in the pathogenicity of A. fumigatus by regulating gliotoxin production during the phagocytosis pathway to overcome the host defense system.

Oxidative Modification of Fibrinogen Affects Its Binding Activity to Glycoprotein (GP) IIb/IIIa

2009 ◽  
Vol 16 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Sermin Tetik ◽  
Kurtulus Kaya ◽  
M. Demir ◽  
Emel Eksioglu-Demiralp ◽  
Turay Yardimci
Keyword(s):  
Metal Ion ◽  
Degradation Products ◽  
Binding Capacity ◽  
Protein Structures ◽  
Human Platelets ◽  
Binding Activity ◽  
Oxidative Modification ◽  
Oxidized Fibrinogen ◽  
Protein Functions

Aim: Proteins are sensitive biomarkers of human diease condition associated with oxidative stress. Alteration of protein structures by oxidants may result in partial or complete loss of protein functions. We have investigated the effect of structural modifications induced by metal ion catalyzed oxidation of fibrinogen on its binding capacity to glycoprotein IIb/IIIa (GpIIb/IIIa) and human platelets. Methods: We identified and quantified of binding capacity of native and oxidized fibrinogen to its receptor in vitro by flow cytometer. Dityrosine formation on oxidized fibrinogen were detected spectrophotometrically. Elevated degradation products of fibrinogen after oxidation were revealed in the HPLC analysis. The native and oxidized fibrinogen were analyzed on mass spectrum upon digestion with tyripsin. Results: Oxidatively modified fibrinogen showed less binding activity than native fibrinogen to GpIIb/IIIa coated micro beads and human platelets whereas slightly higher binding capaticity to ADP induced stimulated platelets. Formation of dityrosines in the amino acid side chains of fibrinogen were observed upon oxidation. Decreased binding capacity of oxidized fibrinogen correlated with intensities of dityrosine formation. Oxidized fibrinogen had more ion-mass intensities at higher than native fibrinogen. Clinical implications: Important point is decreased of binding capacity of the oxidized fibrinogen to own receptor. The decreased rate of binding, leading to effect in the diseases of clot formation may acount for the association between oxidation of fibrinogen and the incidence of effect in human diseases.

scholarly journals A novel DNA-binding motif in the nuclear matrix attachment DNA-binding protein SATB1

1994 ◽  
Vol 14 (3) ◽  
pp. 1852-1860
Author(s):  
K Nakagomi ◽  
Y Kohwi ◽  
L A Dickinson ◽  
T Kohwi-Shigematsu
Keyword(s):  
Amino Acid ◽  
Dna Binding ◽  
Direct Contact ◽  
Binding Protein ◽  
Binding Activity ◽  
Binding Domain ◽  
Binding Motif ◽  
Dna Binding Domain ◽  
Sequence Context ◽  
Dna Binding Activity

The nuclear matrix attachment DNA (MAR) binding protein SATB1 is a sequence context-specific binding protein that binds in the minor groove, making virtually no contact with the DNA bases. The SATB1 binding sites consist of a special AT-rich sequence context in which one strand is well-mixed A's, T's, and C's, excluding G's (ATC sequences), which is typically found in clusters within different MARs. To determine the extent of conservation of the SATB1 gene among different species, we cloned a mouse homolog of the human STAB1 cDNA from a cDNA expression library of the mouse thymus, the tissue in which this protein is predominantly expressed. This mouse cDNA encodes a 764-amino-acid protein with a 98% homology in amino acid sequence to the human SATB1 originally cloned from testis. To characterize the DNA binding domain of this novel class of protein, we used the mouse SATB1 cDNA and delineated a 150-amino-acid polypeptide as the binding domain. This region confers full DNA binding activity, recognizes the specific sequence context, and makes direct contact with DNA at the same nucleotides as the whole protein. This DNA binding domain contains a novel DNA binding motif: when no more than 21 amino acids at either the N- or C-terminal end of the binding domain are deleted, the majority of the DNA binding activity is lost. The concomitant presence of both terminal sequences is mandatory for binding. These two terminal regions consist of hydrophilic amino acids and share homologous sequences that are different from those of any known DNA binding motifs. We propose that the DNA binding region of SATB1 extends its two terminal regions toward DNA to make direct contact with DNA.

scholarly journals Metal ion recognition of the metal-binding motif in hammerhead ribozymes

2003 ◽  
Vol 43 (supplement) ◽  
pp. S28
Author(s):  
Y. Tanaka ◽  
Y. Kasai ◽  
C. Kojima ◽  
K. Yamasaki ◽  
H. Morita ◽  
...  
Keyword(s):  
Metal Binding ◽  
Metal Ion ◽  
Binding Motif ◽  
Hammerhead Ribozymes ◽  
Ion Recognition ◽  
Metal Binding Motif

Studies on copper and cobalt therapy of cattle in central coastal Queensland

1967 ◽  
Vol 18 (1) ◽  
pp. 169 ◽  
Author(s):  
GI Alexander ◽  
JM Harvey ◽  
JH Lee ◽  
WC Stubbs
Keyword(s):  
Growth Response ◽  
Copper Deficiency ◽  
Copper Metabolism ◽  
Subcutaneous Injections ◽  
Liver Copper ◽  
Copper Status ◽  
Period 2 ◽  
Copper Supplementation ◽  
Copper Therapy ◽  
Effect Of Copper

Four experiments described determined the effect of copper and cobalt therapy on the growth and productivity of cattle on the marine plains of central coastal Queensland. Copper was administered by subcutaneous injections of copper glycinate, and cobalt by dosing per os with heavy cobalt pellets. The growth of weaned cattle was significantly improved by copper, particularly from June to October when limited palatable feed on the high ground forced the animals to forage on the para grass swamps. During the same period, 2-year-old heifers also showed a growth response to copper. Their conception rate increased after 19 months of copper therapy but not after 10.5 months. The growth rate of their calves bas significantly increased by copper supplementation. Liver copper concentrations were always low in untreated cattle. Copper therapy maintained these reserves at higher levels, which varied according to the season and the rate of growth of the animals. Calves born to treated cows had higher initial liver copper reserves than those from untreated cows, but in the absence of copper therapy these reserves declined to low and comparable levels in all calves at weaning. Pasture analyses suggest that the copper deficiency revealed was due to interference with copper metabolism rather than to a low copper status in the diet; this interference did not appear to be due to molybdenum. Weaned cattle appeared to respond to cobalt during 1960 but not subsequently, while the cows and calves showed no response. The vitamin B12 status in liver and serum appeared adequate in both treated and untreated cattle.

Theoretical insights into the competitive metal bioaffinity of lactoferrin as a metal ion carrier: a DFT study

2019 ◽  
Vol 43 (41) ◽  
pp. 16374-16384 ◽  
Author(s):  
Bahareh Honarparvar ◽  
Suvardhan Kanchi ◽  
Krishna Bisetty
Keyword(s):  
Metal Ion ◽  
Protein Complexes ◽  
Body Fluids ◽  
Pivotal Role ◽  
Dft Study ◽  
Iron Binding ◽  
Ion Carrier ◽  
Living Organisms ◽  
Binding Glycoprotein

Metal–protein complexes, specifically lactoferrin (Lf), an iron-binding glycoprotein found naturally in milk and several other body fluids play a pivotal role in all living organisms.

Structural elucidation of a dual-activity PAP phosphatase-1 fromEntamoeba histolyticacapable of hydrolysing both 3′-phosphoadenosine 5′-phosphate and inositol 1,4-bisphosphate

2014 ◽  
Vol 70 (7) ◽  
pp. 2019-2031 ◽  
Author(s):  
Khaja Faisal Tarique ◽  
Syed Arif Abdul Rehman ◽  
S. Gourinath
Keyword(s):  
Metal Ions ◽  
Metal Ion ◽  
Genomic Analysis ◽  
Inositol Polyphosphate ◽  
Inositol Monophosphatase ◽  
Native Form ◽  
Catalytic Loop ◽  
Important Regulator ◽  
Living Organisms ◽  
Toxic Byproduct

The enzyme 3′-phosphoadenosine 5′-phosphatase-1 (PAP phosphatase-1) is a member of the Li+-sensitive Mg2+-dependent phosphatase superfamily, or inositol monophosphatase (IMPase) superfamily, and is an important regulator of the sulfate-activation pathway in all living organisms. Inhibition of this enzyme leads to accumulation of the toxic byproduct 3′-phosphoadenosine 5′-phosphate (PAP), which could be lethal to the organism. Genomic analysis ofEntamoeba histolyticasuggests the presence of two isoforms of PAP phosphatase. The PAP phosphatase-1 isoform of this organism is shown to be active over wide ranges of pH and temperature. Interestingly, this enzyme is inhibited by submillimolar concentrations of Li+, while being insensitive to Na+. Interestingly, the enzyme showed activity towards both PAP and inositol 1,4-bisphosphate and behaved as an inositol polyphosphate 1-phosphatase. Crystal structures of this enzyme in its native form and in complex with adenosine 5′-monophosphate have been determined to 2.1 and 2.6 Å resolution, respectively. The PAP phosphatase-1 structure is divided into two domains, namely α+β and α/β, and the substrate and metal ions bind between them. This is a first structure of any PAP phosphatase to be determined from a human parasitic protozoan. This enzyme appears to function using a mechanism involving three-metal-ion assisted catalysis. Comparison with other structures indicates that the sensitivity to alkali-metal ions may depend on the orientation of a specific catalytic loop.

GLOBAL METAL-ION BINDING PROTEIN FINGERPRINT: A METHOD TO IDENTIFY MOTIF-LESS METAL-ION BINDING PROTEINS

2010 ◽  
Vol 08 (04) ◽  
pp. 717-726 ◽  
Author(s):  
ABHILASH MOHAN ◽  
SHARMILA ANISHETTY ◽  
PENNATHUR GAUTAM
Keyword(s):  
Metal Ion ◽  
Binding Proteins ◽  
Binding Protein ◽  
Vital Role ◽  
Ion Binding ◽  
Binding Motif ◽  
Specific Class ◽  
Metal Ion Binding ◽  
Knowledge Based ◽  
Supervised Classifiers

Metal-ion binding proteins play a vital role in biological processes. Identifying putative metal-ion binding proteins is through knowledge-based methods. These involve the identification of specific motifs that characterize a specific class of metal-ion binding protein. Metal-ion binding motifs have been identified for the common metal ions. A robust global fingerprint that is useful in identifying a metal-ion binding protein from a non-metal-ion binding protein has not been devised. Such a method will help in identifying novel metal-ion binding proteins and proteins that do not possess a canonical metal-ion binding motif. We have used a set of physico-chemical parameters of metal-ion binding proteins encoded by the genes CzcA, CzcB and CzcD as a training set to supervised classifiers and have been able to identify several other metal ion binding proteins leading us to believe that metal-ion binding proteins have a global fingerprint, which cannot be pinned down to a single feature of the protein sequence.

Cellular copper homeostasis: current concepts on its interplay with glutathione homeostasis and its implication in physiology and human diseases

Metallomics ◽  
2017 ◽  
Vol 9 (10) ◽  
pp. 1376-1388 ◽  
Author(s):  
Ashima Bhattacharjee ◽  
Kaustav Chakraborty ◽  
Aditya Shukla
Keyword(s):  
Trace Element ◽  
Copper Homeostasis ◽  
Human Diseases ◽  
Living Organisms ◽  
Cellular Copper ◽  
Almost All ◽  
Glutathione Homeostasis ◽  
Intracellular Copper

Copper is a trace element essential for almost all living organisms, however the level of intracellular copper needs to be tightly regulated. This review explores the existing literature on the role of glutathione in regulating cellular copper homeostasis.

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