scholarly journals Sonic Hedgehog is a member of the Hh/DD-peptidase family that spans the eukaryotic and bacterial domains of life

2018 ◽  
Author(s):  
Henk Roelink
Keyword(s):  
Catalytic Activity ◽  
Sonic Hedgehog ◽  
Birth Defect ◽  
Bacterial Gene ◽  
Bacterial Proteins ◽  
Gene Coding ◽  
Domains Of Life ◽  
Hh Signaling ◽  
Congenital Birth Defect ◽  
Stable Forms

AbstractSonic Hedgehog (Shh) coordinates Zn2+ in a manner that resembles that of peptidases. The ability of Shh to undergo autoproteolytic processing is impaired in mutants that affect the Zn2+ coordination, while mutating residues essential for catalytic activity results in more stable forms of Shh. The residues involved in Zn2+ coordination in Shh are found mutated in some individuals with the congenital birth defect holoprosencephaly, demonstrating their importance in development. Highly conserved Shh domains are found a parts of some bacterial proteins that are members of the larger family of DD-peptidases, supporting the notion that Shh acts as a peptidase. Whereas this Hh/DD-peptidase motif is present in Hedgehog (Hh) proteins of nearly all animals, it is not present in Drosophila Hh, indicating that Hh signaling in fruit flies is derived, and perhaps not a good model for vertebrate Shh signaling. Sequence analysis of Hh proteins and their possible evolutionary precursors suggest that the evolution of modern Hh might have involved horizontal transfer of a bacterial gene coding of a Hh/DD-peptidase into a Cnidarian ancestor, recombining to give rise to modern Hh.

scholarly journals Metabolic Engineering of Fungal Strains for Conversion of d-Galacturonate to meso-Galactarate

2009 ◽  
Vol 76 (1) ◽  
pp. 169-175 ◽  
Author(s):  
Dominik Mojzita ◽  
Marilyn Wiebe ◽  
Satu Hilditch ◽  
Harry Boer ◽  
Merja Penttilä ◽  
...  
Keyword(s):  
Metabolic Engineering ◽  
Aspergillus Niger ◽  
Galacturonic Acid ◽  
Raw Material ◽  
High Yield ◽  
Hypocrea Jecorina ◽  
Bacterial Gene ◽  
Fungal Strains ◽  
Gene Coding ◽  
Reductive Pathway

ABSTRACT d-Galacturonic acid can be obtained by hydrolyzing pectin, which is an abundant and low value raw material. By means of metabolic engineering, we constructed fungal strains for the conversion of d-galacturonate to meso-galactarate (mucate). Galactarate has applications in food, cosmetics, and pharmaceuticals and as a platform chemical. In fungi d-galacturonate is catabolized through a reductive pathway with a d-galacturonate reductase as the first enzyme. Deleting the corresponding gene in the fungi Hypocrea jecorina and Aspergillus niger resulted in strains unable to grow on d-galacturonate. The genes of the pathway for d-galacturonate catabolism were upregulated in the presence of d-galacturonate in A. niger, even when the gene for d-galacturonate reductase was deleted, indicating that d-galacturonate itself is an inducer for the pathway. A bacterial gene coding for a d-galacturonate dehydrogenase catalyzing the NAD-dependent oxidation of d-galacturonate to galactarate was introduced to both strains with disrupted d-galacturonate catabolism. Both strains converted d-galacturonate to galactarate. The resulting H. jecorina strain produced galactarate at high yield. The A. niger strain regained the ability to grow on d-galacturonate when the d-galacturonate dehydrogenase was introduced, suggesting that it has a pathway for galactarate catabolism.

scholarly journals Complex method of the prognosis of tick-born neuroinfections

2008 ◽  
Vol 7 (5-2) ◽  
pp. 420-423
Author(s):  
A. V. Subbotin ◽  
V. A. Semyonov ◽  
I. Yu. Torshin ◽  
O. A. Gromova ◽  
Ye. V. Fyodorova ◽  
...  
Keyword(s):  
Immune Response ◽  
Risk Factor ◽  
Catalytic Activity ◽  
Rna Viruses ◽  
Clinical Manifestations ◽  
Important Risk Factor ◽  
Biochemical Data ◽  
Complex Method ◽  
Gene Coding ◽  
Tick Borne Encephalitis

Here, we propose a method of forecasting the development of the heavy forms of the tick-borne encephalitis using diagnostic tables. The method is based on evaluation of the patients with syndrome of endogenous intoxication using immunological and biochemical data along with evaluation of the clinical manifestations. We also propose an advanced form of the method that includes data based on the genotype of OAS1 — the gene, coding oligonucleotidesynthetase needed for immune response to RNA viruses. OAS1 genotype is an important risk factor since the differences in catalytic activity of OAS1 isoenzymes result in different susceptibility to the virus of the tick-borne encephalitis.

scholarly journals Gene-teratogen interactions influence the penetrance of birth defects by altering Hedgehog signaling strength

Development ◽  
2021 ◽  
Vol 148 (19) ◽  
Author(s):  
Jennifer H. Kong ◽  
Cullen B. Young ◽  
Ganesh V. Pusapati ◽  
F. Hernán Espinoza ◽  
Chandni B. Patel ◽  
...  
Keyword(s):  
Small Molecules ◽  
Birth Defects ◽  
Birth Defect ◽  
Hedgehog Signaling ◽  
Multiple Birth ◽  
In Utero Exposure ◽  
Membrane Protein Complex ◽  
Protein Target ◽  
Hh Signaling ◽  
Genetic And Environmental Factors

ABSTRACT Birth defects result from interactions between genetic and environmental factors, but the mechanisms remain poorly understood. We find that mutations and teratogens interact in predictable ways to cause birth defects by changing target cell sensitivity to Hedgehog (Hh) ligands. These interactions converge on a membrane protein complex, the MMM complex, that promotes degradation of the Hh transducer Smoothened (SMO). Deficiency of the MMM component MOSMO results in elevated SMO and increased Hh signaling, causing multiple birth defects. In utero exposure to a teratogen that directly inhibits SMO reduces the penetrance and expressivity of birth defects in Mosmo−/− embryos. Additionally, tissues that develop normally in Mosmo−/− embryos are refractory to the teratogen. Thus, changes in the abundance of the protein target of a teratogen can change birth defect outcomes by quantitative shifts in Hh signaling. Consequently, small molecules that re-calibrate signaling strength could be harnessed to rescue structural birth defects.

scholarly journals Ontogenic expression of a CyI actin fusion gene injected into sea urchin eggs

Development ◽  
1987 ◽  
Vol 101 (3) ◽  
pp. 437-447
Author(s):  
K.S. Katula ◽  
B.R. Hough-Evans ◽  
R.J. Britten ◽  
E.H. Davidson
Keyword(s):  
Sea Urchin ◽  
Fusion Gene ◽  
Transcription Unit ◽  
Upstream Region ◽  
Upstream Sequence ◽  
Flanking Sequence ◽  
Bacterial Gene ◽  
Fusion Construct ◽  
Gene Coding ◽  
Sea Urchin Egg

The 5′ terminus of the CyI actin gene transcription unit of Strongylocentrotus purpuratus was located by primer extension and other procedures, and the flanking upstream region was partially sequenced and mapped. A fusion gene was constructed containing about 2.5 kb of 5′ flanking sequence, the transcribed leader sequence, and the first few codons of the CyI gene ligated to the bacterial gene coding for chloramphenicol acetyl transferase (CAT). This was micro-injected into the cytoplasm of S. purpuratus eggs, and CAT enzyme activity was measured at various stages of embryonic development. CAT synthesis was activated between 10 and 14 h postfertilization, the same time at which newly synthesized transcripts of the endogenous CyI gene first appear. The exogenous CyI.CAT fusion DNA replicated actively during cleavage, as observed previously for other DNAs injected into sea urchin egg cytoplasm. Thus the absence of CAT activity prior to 10 h postfertilization could not be due to insufficient CyI.CAT genes. The amounts of CAT enzyme produced by embryos bearing CyI.CAT deletions that lack various regions of the CyI sequence were measured. As little as 254 nucleotides of upstream CyI sequence suffice for correct temporal activation of the fusion construct, although the level of CAT enzyme produced in embryos bearing any deletion retaining less than 850 nucleotides of upstream sequence was significantly lowered compared to controls bearing the complete CyI.CAT fusion construct.

Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation

2001 ◽  
Vol 114 (11) ◽  
pp. 2085-2094 ◽  
Author(s):  
Sylviane Spinella-Jaegle ◽  
Georges Rawadi ◽  
Shinji Kawai ◽  
Sylvie Gallea ◽  
Chi Faucheu ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Inverse Relationship ◽  
Mesenchymal Cell ◽  
Bone Morphogenetic Protein 2 ◽  
Short Treatment ◽  
Morphogenetic Protein ◽  
Adipocytic Differentiation ◽  
Hh Signaling ◽  
Transcriptional Output ◽  
Calvaria Cell

The proteins of the hedgehog (Hh) family regulate various aspects of development. Recently, members of this family have been shown to regulate skeletal formation in vertebrates and to control both chondrocyte and osteoblast differentiation. In the present study, we analyzed the effect of Sonic hedgehog (Shh) on the osteoblastic and adipocytic commitment/differentiation. Recombinant N-terminal Shh (N-Shh) significantly increased the percentage of both the pluripotent mesenchymal cell lines C3H10T1/2 and ST2 and calvaria cells responding to bone morphogenetic protein 2 (BMP-2), in terms of osteoblast commitment as assessed by measuring alkaline phosphatase (ALP) activity. This synergistic effect was mediated, at least partly, through the positive modulation of the transcriptional output of BMPs via Smad signaling. Furthermore, N-Shh was found to abolish adipocytic differentiation of C3H10T1/2 cells both in the presence or absence of BMP-2. A short treatment with N-Shh was sufficient to dramatically reduce the levels of the adipocytic-related transcription factors C/EBPα and PPARγ in both C3H10T1/2 and calvaria cell cultures. Given the inverse relationship between marrow adipocytes and osteoblasts with aging, agonists of the Hh signaling pathway might constitute potential drugs for preventing and/or treating osteopenic disorders.

Expression in Plants of a Bacterial Gene Coding for Glyphosate Resistance

Weed Science ◽  
1987 ◽  
Vol 35 (S1) ◽  
pp. 19-23 ◽  
Author(s):  
Gregory A. Thompson ◽  
William R. Hiatt ◽  
Daniel Facciotti ◽  
David M. Stalker ◽  
Luca Comai
Keyword(s):  
Single Amino Acid ◽  
Kinetic Properties ◽  
Epsp Synthase ◽  
Bacterial Gene ◽  
Gene Coding ◽  
Bacterial Enzyme ◽  
Genetically Engineer ◽  
Single Amino Acid Change ◽  
Low Sensitivity ◽  
Dna Vectors

The target site of glyphosate [N-(phosphonomethyl)glycine] inhibition in plants and bacteria is 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase. Our strategy for developing glyphosate-resistant crops has been to genetically engineer plants with a gene that codes for EPSP synthase with low sensitivity in glyphosate. We cloned such a gene from thearoAlocus of a glyphosate-resistant mutagenized strain ofSalmonella typhimurium.The enzyme encoded by this gene has a single amino acid change resulting in lower affinity for glyphosate and higher affinity for substrates than either plant or wild-type bacterial counterpart. A chimaeric gene containing the mutantaroAgene behind the octopine synthase promoter was constructed and integrated intoAgrobacteriumT-DNA vectors. Analysis of gall tissue fromBrassica campestrisL. (turnip rape) infected withA. tumefaciensK12 containing this chimaera showed mRNA and protein expressed from the bacterial gene; 50% of the total EPSP synthase activity present had kinetic properties of the mutant bacterial enzyme. Tobacco (Nicotiana tabacumL. ‘Xanthi′) plants have been regenerated from cocultivation withA. rhizogenescontaining the same construct; analysis indicates expression of the gene and enhanced tolerance to glyphosate.

scholarly journals Hedgehog proteins create a dynamic cholesterol interface

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246814 ◽  
Author(s):  
Amirhossein Mafi ◽  
Rahul Purohit ◽  
Erika Vielmas ◽  
Alexa R. Lauinger ◽  
Brandon Lam ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Sonic Hedgehog ◽  
Tissue Regeneration ◽  
Molecular Basis ◽  
Signaling Proteins ◽  
Full Structure ◽  
Hedgehog Proteins ◽  
Hh Signaling ◽  
Dynamics Simulations ◽  
Photoaffinity Crosslinking

During formation of the Hedgehog (Hh) signaling proteins, cooperative activities of the Hedgehog INTein (Hint) fold and Sterol Recognition Region (SRR) couple autoproteolysis to cholesterol ligation. The cholesteroylated Hh morphogens play essential roles in embryogenesis, tissue regeneration, and tumorigenesis. Despite the centrality of cholesterol in Hh function, the full structure of the Hint-SRR (“Hog”) domain that attaches cholesterol to the last residue of the active Hh morphogen remains enigmatic. In this work, we combine molecular dynamics simulations, photoaffinity crosslinking, and mutagenesis assays to model cholesterolysis intermediates in the human Sonic Hedgehog (hSHH) protein. Our results provide evidence for a hydrophobic Hint-SRR interface that forms a dynamic, non-covalent cholesterol-Hog complex. Using these models, we suggest a unified mechanism by which Hh proteins can recruit, sequester, and orient cholesterol, and offer a molecular basis for the effects of disease-causing hSHH mutations.

scholarly journals The catalytic activity of the translation termination factor methyltransferase Mtq2-Trm112 complex is required for large ribosomal subunit biogenesis

2020 ◽  
Vol 48 (21) ◽  
pp. 12310-12325
Author(s):  
Caroline Lacoux ◽  
Ludivine Wacheul ◽  
Kritika Saraf ◽  
Nicolas Pythoud ◽  
Emmeline Huvelle ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Ribosome Biogenesis ◽  
Translation Termination ◽  
Ribosomal Subunit ◽  
Efficient Production ◽  
Large Ribosomal Subunit ◽  
Termination Factor ◽  
Domains Of Life ◽  
Quality Control Mechanism ◽  
Translation Termination Factor

Abstract The Mtq2-Trm112 methyltransferase modifies the eukaryotic translation termination factor eRF1 on the glutamine side chain of a universally conserved GGQ motif that is essential for release of newly synthesized peptides. Although this modification is found in the three domains of life, its exact role in eukaryotes remains unknown. As the deletion of MTQ2 leads to severe growth impairment in yeast, we have investigated its role further and tested its putative involvement in ribosome biogenesis. We found that Mtq2 is associated with nuclear 60S subunit precursors, and we demonstrate that its catalytic activity is required for nucleolar release of pre-60S and for efficient production of mature 5.8S and 25S rRNAs. Thus, we identify Mtq2 as a novel ribosome assembly factor important for large ribosomal subunit formation. We propose that Mtq2-Trm112 might modify eRF1 in the nucleus as part of a quality control mechanism aimed at proof-reading the peptidyl transferase center, where it will subsequently bind during translation termination.

scholarly journals Serum Bisphenol A Level in Boys with Cryptorchidism: A Step to Male Infertility?

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Marta Diana Komarowska ◽  
Adam Hermanowicz ◽  
Urszula Czyzewska ◽  
Robert Milewski ◽  
Ewa Matuszczak ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Birth Defect ◽  
Undescended Testis ◽  
Serum Levels ◽  
High Serum ◽  
Positive Answer ◽  
Total Serum ◽  
Control Group ◽  
Congenital Birth Defect ◽  
Free Serum

Cryptorchidism is the most common congenital birth defect in boys and affects about 2–4% full-term male neonates. Its etiology is multifactorial.Purpose. To evaluate the serum bisphenol A (BPA) levels in boys with cryptorchidism and healthy boys and to assess the risk of environmental exposure to BPA using the authors’ questionnaire. The data were acquired from a study on boys with cryptorchidism (n=98) and a control group (n=57). Prior to surgery, all patients had BPA serum levels evaluated. The size, position, rigidity of the testis, and abnormality of the epididymis of the undescended testis were assessed. Parents also completed a questionnaire on the risks of exposure to BPA in everyday life.Results. The testes in both groups were similar in size. The turgor of the undescended testis in the group of boys with cryptorchidism was decreased. Free serum BPA level in cryptorchid boys and in the control group was not statistically significant (p>0.05). The conjugated serum BPA level in cryptorchid boys and in the control group was statistically significant (p≤0.05). Total serum BPA level in cryptorchid boys and in the control group was statistically significant (p<0.05). Serum total BPA level was related with a positive answer about problems with conception (p<0.02).Conclusion. Our study indicated that high serum BPA was associated with cryptorchidism.

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