scholarly journals Mammalian molybdo-flavoenzymes, an expanding family of proteins: structure, genetics, regulation, function and pathophysiology

2003 ◽  
Vol 372 (1) ◽  
pp. 15-32 ◽  
Author(s):  
Enrico GARATTINI ◽  
Ralf MENDEL ◽  
Maria João ROMÃO ◽  
Richard WRIGHT ◽  
Mineko TERAO
Keyword(s):  
Current Knowledge ◽  
Aldehyde Oxidase ◽  
Amino Acid Sequences ◽  
Xanthine Oxidoreductase ◽  
Mechanism Of Catalysis ◽  
Key Enzyme ◽  
Regulation Function ◽  
A Cell ◽  
Endogenous Substrate ◽  
Related Proteins

The molybdo–flavoenzymes are structurally related proteins that require a molybdopterin cofactor and FAD for their catalytic activity. In mammals, four enzymes are known: xanthine oxidoreductase, aldehyde oxidase and two recently described mouse proteins known as aldehyde oxidase homologue 1 and aldehyde oxidase homologue 2. The present review article summarizes current knowledge on the structure, enzymology, genetics, regulation and pathophysiology of mammalian molybdo–flavoenzymes. Molybdo–flavoenzymes are structurally complex oxidoreductases with an equally complex mechanism of catalysis. Our knowledge has greatly increased due to the recent crystallization of two xanthine oxidoreductases and the determination of the amino acid sequences of many members of the family. The evolution of molybdo–flavoenzymes can now be traced, given the availability of the structures of the corresponding genes in many organisms. The genes coding for molybdo–flavoenzymes are expressed in a cell-specific fashion and are controlled by endogenous and exogenous stimuli. The recent cloning of the genes involved in the biosynthesis of the molybdenum cofactor has increased our knowledge on the assembly of the apo-forms of molybdo–flavoproteins into the corresponding holo-forms. Xanthine oxidoreductase is the key enzyme in the catabolism of purines, although recent data suggest that the physiological function of this enzyme is more complex than previously assumed. The enzyme has been implicated in such diverse pathological situations as organ ischaemia, inflammation and infection. At present, very little is known about the pathophysiological relevance of aldehyde oxidase, aldehyde oxidase homologue 1 and aldehyde oxidase homologue 2, which do not as yet have an accepted endogenous substrate.

scholarly journals Sporulation in solventogenic and acetogenic clostridia

2021 ◽  
Author(s):  
Mamou Diallo ◽  
Servé W. M. Kengen ◽  
Ana M. López-Contreras
Keyword(s):  
Current Knowledge ◽  
Carbon Sources ◽  
Cost Effective ◽  
Biotechnological Production ◽  
Key Points ◽  
Wide Range ◽  
Potential Applications ◽  
A Cell ◽  
Sporulation Initiation ◽  
Solventogenic Clostridia

AbstractThe Clostridium genus harbors compelling organisms for biotechnological production processes; while acetogenic clostridia can fix C1-compounds to produce acetate and ethanol, solventogenic clostridia can utilize a wide range of carbon sources to produce commercially valuable carboxylic acids, alcohols, and ketones by fermentation. Despite their potential, the conversion by these bacteria of carbohydrates or C1 compounds to alcohols is not cost-effective enough to result in economically viable processes. Engineering solventogenic clostridia by impairing sporulation is one of the investigated approaches to improve solvent productivity. Sporulation is a cell differentiation process triggered in bacteria in response to exposure to environmental stressors. The generated spores are metabolically inactive but resistant to harsh conditions (UV, chemicals, heat, oxygen). In Firmicutes, sporulation has been mainly studied in bacilli and pathogenic clostridia, and our knowledge of sporulation in solvent-producing or acetogenic clostridia is limited. Still, sporulation is an integral part of the cellular physiology of clostridia; thus, understanding the regulation of sporulation and its connection to solvent production may give clues to improve the performance of solventogenic clostridia. This review aims to provide an overview of the triggers, characteristics, and regulatory mechanism of sporulation in solventogenic clostridia. Those are further compared to the current knowledge on sporulation in the industrially relevant acetogenic clostridia. Finally, the potential applications of spores for process improvement are discussed.Key Points• The regulatory network governing sporulation initiation varies in solventogenic clostridia.• Media composition and cell density are the main triggers of sporulation.• Spores can be used to improve the fermentation process.

scholarly journals Identification of persulfide-binding and disulfide-forming cysteine residues in the NifS-like domain of the molybdenum cofactor sulfurase ABA3 by cysteine-scanning mutagenesis

2012 ◽  
Vol 441 (3) ◽  
pp. 823-839 ◽  
Author(s):  
Markus Lehrke ◽  
Steffen Rump ◽  
Torsten Heidenreich ◽  
Josef Wissing ◽  
Ralf R. Mendel ◽  
...  
Keyword(s):  
Structural Model ◽  
Bond Distance ◽  
Aldehyde Oxidase ◽  
Disulfide Bridge ◽  
Cysteine Residue ◽  
Molybdenum Cofactor ◽  
Cysteine Residues ◽  
Xanthine Oxidoreductase ◽  
Cysteine Scanning Mutagenesis ◽  
Molybdenum Cofactor Sulfurase

The Moco (molybdenum cofactor) sulfurase ABA3 from Arabidopsis thaliana catalyses the sulfuration of the Moco of aldehyde oxidase and xanthine oxidoreductase, which represents the final activation step of these enzymes. ABA3 consists of an N-terminal NifS-like domain that exhibits L-cysteine desulfurase activity and a C-terminal domain that binds sulfurated Moco. The strictly conserved Cys430 in the NifS-like domain binds a persulfide intermediate, which is abstracted from the substrate L-cysteine and finally needs to be transferred to the Moco of aldehyde oxidase and xanthine oxidoreductase. In addition to Cys430, another eight cysteine residues are located in the NifS-like domain, with two of them being highly conserved among Moco sulfurase proteins and, at the same time, being in close proximity to Cys430. By determination of the number of surface-exposed cysteine residues and the number of persulfide-binding cysteine residues in combination with the sequential substitution of each of the nine cysteine residues, a second persulfide-binding cysteine residue, Cys206, was identified. Furthermore, the active-site Cys430 was found to be located on top of a loop structure, formed by the two flanking residues Cys428 and Cys435, which are likely to form an intramolecular disulfide bridge. These findings are confirmed by a structural model of the NifS-like domain, which indicates that Cys428 and Cys435 are within disulfide bond distance and that a persulfide transfer from Cys430 to Cys206 is indeed possible.

scholarly journals In-silicoprediction and modeling of theEntamoeba histolyticaproteins: Serine-richEntamoeba histolyticaprotein and 29 kDa Cysteine-rich protease

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3160 ◽  
Author(s):  
Kumar Manochitra ◽  
Subhash Chandra Parija
Keyword(s):  
Amino Acid ◽  
Structure Prediction ◽  
Tertiary Structure ◽  
Protein Structures ◽  
Amino Acid Sequences ◽  
Treatment Modalities ◽  
Bioinformatic Tools ◽  
Complex Protein ◽  
A Cell ◽  
Quaternary Structures

BackgroundAmoebiasis is the third most common parasitic cause of morbidity and mortality, particularly in countries with poor hygienic settings. There exists an ambiguity in the diagnosis of amoebiasis, and hence there arises a necessity for a better diagnostic approach. Serine-richEntamoeba histolyticaprotein (SREHP), peroxiredoxin and Gal/GalNAc lectin are pivotal inE. histolyticavirulence and are extensively studied as diagnostic and vaccine targets. For elucidating the cellular function of these proteins, details regarding their respective quaternary structures are essential. However, studies in this aspect are scant. Hence, this study was carried out to predict the structure of these target proteins and characterize them structurally as well as functionally using appropriatein-silicomethods.MethodsThe amino acid sequences of the proteins were retrieved from National Centre for Biotechnology Information database and aligned using ClustalW. Bioinformatic tools were employed in the secondary structure and tertiary structure prediction. The predicted structure was validated, and final refinement was carried out.ResultsThe protein structures predicted by i-TASSER were found to be more accurate than Phyre2 based on the validation using SAVES server. The prediction suggests SREHP to be an extracellular protein, peroxiredoxin a peripheral membrane protein while Gal/GalNAc lectin was found to be a cell-wall protein. Signal peptides were found in the amino-acid sequences of SREHP and Gal/GalNAc lectin, whereas they were not present in the peroxiredoxin sequence. Gal/GalNAc lectin showed better antigenicity than the other two proteins studied. All the three proteins exhibited similarity in their structures and were mostly composed of loops.DiscussionThe structures of SREHP and peroxiredoxin were predicted successfully, while the structure of Gal/GalNAc lectin could not be predicted as it was a complex protein composed of sub-units. Also, this protein showed less similarity with the available structural homologs. The quaternary structures of SREHP and peroxiredoxin predicted from this study would provide better structural and functional insights into these proteins and may aid in development of newer diagnostic assays or enhancement of the available treatment modalities.

scholarly journals The yeast omnipotent suppressor SUP46 encodes a ribosomal protein which is a functional and structural homolog of the Escherichia coli S4 ram protein.

Genetics ◽  
1992 ◽  
Vol 132 (2) ◽  
pp. 375-386 ◽  
Author(s):  
A Vincent ◽  
S W Liebman
Keyword(s):  
Escherichia Coli ◽  
Ribosomal Protein ◽  
Dna Sequences ◽  
Ribosomal Proteins ◽  
Amino Acid Sequences ◽  
Ribosomal Protein Genes ◽  
Significant Homology ◽  
A Cell ◽  
Functional Equivalent ◽  
Ribosomal Protein S13

Abstract The accurate synthesis of proteins is crucial to the existence of a cell. In yeast, several genes that affect the fidelity of translation have been identified (e.g., omnipotent suppressors, antisuppressors and allosuppressors). We have found that the dominant omnipotent suppressor SUP46 encodes the yeast ribosomal protein S13. S13 is encoded by two similar genes, but only the sup46 copy of the gene is able to fully complement the recessive phenotypes of SUP46 mutations. Both copies of the S13 genes contain introns. Unlike the introns of other duplicated ribosomal protein genes which are highly diverged, the duplicated S13 genes have two nearly identical DNA sequences of 25 and 31 bp in length within their introns. The SUP46 protein has significant homology to the S4 ribosomal protein in prokaryotic-type ribosomes. S4 is encoded by one of the ram (ribosomal ambiguity) genes in Escherichia coli which are the functional equivalent of omnipotent suppressors in yeast. Thus, SUP46 and S4 demonstrate functional as well as sequence conservation between prokaryotic and eukaryotic ribosomal proteins. SUP46 and S4 are most similar in their central amino acid sequences. Interestingly, the alterations resulting from the SUP46 mutations and the segment of the S4 protein involved in binding to the 16S rRNA are within this most conserved region.

scholarly journals THE TIME OF SYNTHESIS AND THE CONSERVATION OF MITOSIS-RELATED PROTEINS IN CULTURED HUMAN AMNION CELLS

1967 ◽  
Vol 34 (1) ◽  
pp. 97-110 ◽  
Author(s):  
Jesse E. Sisken ◽  
Elaina Wilkes
Keyword(s):  
Time Lapse ◽  
Major Effect ◽  
Human Amnion ◽  
Daughter Cells ◽  
Low Concentrations ◽  
Associated Proteins ◽  
A Cell ◽  
Quantitative Analyses ◽  
Related Proteins ◽  
Kinetics Of

p-Fluorophenylalanine (PFPA), an analogue of phenylalanine which may be incorporated into proteins, increases the duration of mitosis. In the present experiments, based upon quantitative analyses of time-lapse cinemicrographic films, brief treatments of cells with PFPA are shown to affect the duration of metaphase in only those cells which enter division during or shortly after treatment. The offspring of cells with prolonged metaphases also tend to have prolonged metaphases. Analyses of the kinetics of the appearance of prolonged metaphases indicate that some protein specifically associated with mitosis is synthesized primarily during a period which corresponds closely to G2. The manner in which the defect is passed on to daughter cells indicates that the protein involved is conserved and reutilized by daughter cells for their subsequent divisions. Comparable experiments performed with low concentrations of puromycin indicate that the major effect of PFPA is due to its incorporation into protein rather than its ability to inhibit protein synthesis. The fact that puromycin-induced effects can also be passed on to daughter cells is interpreted to mean that cells make only specific amounts of some mitosis-associated proteins and that if a cell "inherits" a deficiency in such protein it is not able to compensate for the deficiency.

Characterization of a novel promoter insertion in the c-rel locus

1990 ◽  
Vol 10 (9) ◽  
pp. 4788-4794
Author(s):  
N Kabrun ◽  
N Bumstead ◽  
M J Hayman ◽  
P J Enrietto
Keyword(s):  
Molecular Weight ◽  
Alternative Splicing ◽  
Structural Data ◽  
Wild Type ◽  
Repeat Sequences ◽  
Myc Gene ◽  
A Cell ◽  
Related Proteins ◽  
Genetic Events

Avian leukosis virus (ALV)-induced neoplasias are commonly found associated with integrations of proviral DNA in proximity to the myc gene. However, studies suggest that other genetic events are necessary for the complete neoplastic phenotype. A cell line (HP46) derived from an ALV-induced tumor has been analyzed and found to contain, in addition to an alteration in the myc gene, a promoter insertion in the c-rel locus. Both loci expressed large amounts of mRNA coding for their respective proteins. Several rel-related transcripts were expressed in the HP46 line, and four rel-related proteins of lower molecular weight than the wild-type p68c-rel product were detected. At least two of these transcripts contained U5 long terminal repeat sequences on the 5' end of the RNA. Structural data suggest that the messages may have evolved by an alternative splicing mechanism. This is the first example of a promoter insertion in the c-rel locus, a gene whose viral counterpart v-rel is responsible for the induction of lymphoid tumors.

Assembling Blocks

1999 ◽  
Author(s):  
Jorja G. Henikoff
Keyword(s):  
Multiple Alignment ◽  
Amino Acid Sequences ◽  
Individual Sequences ◽  
Protein Group ◽  
Genomic Studies ◽  
Function Blocks ◽  
The Subject ◽  
Comprehensive Evaluations ◽  
Block Width ◽  
Related Proteins

A block is an ungapped local multiple alignment of amino acid sequences from a group of related proteins. Ideally, the contiguous stretch of residues represented by a block is conserved for biological function. Blocks have depth (the number of sequences) and width (the number of aligned positions). There are currently several useful programs for finding blocks in a group of related sequences that I do not discuss in detail here. Among these, Motif (Smith et al., 1990) and Asset (Neuwald and Green, 1994) both align blocks on occurrences of certain types of patterns found in the sequences; Gibbs (Lawrence et al., 1993; Neuwald et al., 1995) and MEME (Bailey and Elkan, 1994) both look for statistically optimal local alignments; and Macaw (Schuler et al., 1991) and Somap (Parry-Smith and Attwood, 1992) both give the user assistance in finding blocks interactively. After candidate blocks are identified by a block-finding method, they can be evaluated and assembled into a set representing the protein group, resulting in a multiple alignment consisting of ungapped regions separated by unaligned regions of variable length. The block assembly process is the subject of this chapter. Both the Blocks (Henikoff and Henikoff, 1996a) and Prints (Attwood and Beck, 1994) databases consist of such sets of blocks and between them currently represent 1,163 different protein groups. These collections of blocks are more sensitive and efficient for classifying new sequences into known protein groups than are collections of individual sequences, as demonstrated by comprehensive evaluations (Henikoff and Henikoff, 1994b, 1997), by genomic studies (Green et al., 1993), and by individual studies (Posfai et al., 1988; Henikoff, 1992, 1993; Attwood and Findlay, 1993; Pietrokovski, 1994; Brown, 1995). Issues that must be addressed during block assembly include the number of blocks provided to the assembly module by the block finders, block width, the number of times a block occurs in each sequence (zero to many), overlap of blocks, and the order of multiple blocks within each sequence. Once these issues are decided, it is necessary to score individual competing blocks and then competing sets of blocks.

scholarly journals S-Nitrosoglutathione Reductase—The Master Regulator of Protein S-Nitrosation in Plant NO Signaling

Plants ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 48 ◽  
Author(s):  
Jana Jahnová ◽  
Lenka Luhová ◽  
Marek Petřivalský
Keyword(s):  
Stress Responses ◽  
Current Knowledge ◽  
Protein S ◽  
Defense Responses ◽  
Reactive Nitrogen ◽  
Cellular Processes ◽  
Protein Thiols ◽  
Key Enzyme ◽  
No Signaling ◽  
Cysteine Thiols

S-nitrosation has been recognized as an important mechanism of protein posttranslational regulations, based on the attachment of a nitroso group to cysteine thiols. Reversible S-nitrosation, similarly to other redox-base modifications of protein thiols, has a profound effect on protein structure and activity and is considered as a convergence of signaling pathways of reactive nitrogen and oxygen species. In plant, S-nitrosation is involved in a wide array of cellular processes during normal development and stress responses. This review summarizes current knowledge on S-nitrosoglutathione reductase (GSNOR), a key enzyme which regulates intracellular levels of S-nitrosoglutathione (GSNO) and indirectly also of protein S-nitrosothiols. GSNOR functions are mediated by its enzymatic activity, which catalyzes irreversible GSNO conversion to oxidized glutathione within the cellular catabolism of nitric oxide. GSNOR is involved in the maintenance of balanced levels of reactive nitrogen species and in the control of cellular redox state. Multiple functions of GSNOR in plant development via NO-dependent and -independent signaling mechanisms and in plant defense responses to abiotic and biotic stress conditions have been uncovered. Extensive studies of plants with down- and upregulated GSNOR, together with application of transcriptomics and proteomics approaches, seem promising for new insights into plant S-nitrosothiol metabolism and its regulation.

scholarly journals Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular

2020 ◽  
Vol 21 (7) ◽  
pp. 2576 ◽  
Author(s):  
Sandra Buratta ◽  
Brunella Tancini ◽  
Krizia Sagini ◽  
Federica Delo ◽  
Elisabetta Chiaradia ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cell Communication ◽  
Lysosomal Storage ◽  
Cellular Processes ◽  
Age Related ◽  
Extracellular Release ◽  
A Cell ◽  
Endosomal System

Beyond the consolidated role in degrading and recycling cellular waste, the autophagic- and endo-lysosomal systems play a crucial role in extracellular release pathways. Lysosomal exocytosis is a process leading to the secretion of lysosomal content upon lysosome fusion with plasma membrane and is an important mechanism of cellular clearance, necessary to maintain cell fitness. Exosomes are a class of extracellular vesicles originating from the inward budding of the membrane of late endosomes, which may not fuse with lysosomes but be released extracellularly upon exocytosis. In addition to garbage disposal tools, they are now considered a cell-to-cell communication mechanism. Autophagy is a cellular process leading to sequestration of cytosolic cargoes for their degradation within lysosomes. However, the autophagic machinery is also involved in unconventional protein secretion and autophagy-dependent secretion, which are fundamental mechanisms for toxic protein disposal, immune signalling and pathogen surveillance. These cellular processes underline the crosstalk between the autophagic and the endosomal system and indicate an intersection between degradative and secretory functions. Further, they suggest that the molecular mechanisms underlying fusion, either with lysosomes or plasma membrane, are key determinants to maintain cell homeostasis upon stressing stimuli. When they fail, the accumulation of undigested substrates leads to pathological consequences, as indicated by the involvement of autophagic and lysosomal alteration in human diseases, namely lysosomal storage disorders, age-related neurodegenerative diseases and cancer. In this paper, we reviewed the current knowledge on the functional role of extracellular release pathways involving lysosomes and the autophagic- and endo-lysosomal systems, evaluating their implication in health and disease.

scholarly journals Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 927 ◽  
Author(s):  
Justine Habault ◽  
Jean-Luc Poyet
Keyword(s):  
Tissue Specificity ◽  
Chemical Compounds ◽  
Drug Carriers ◽  
Cell Penetrating Peptides ◽  
Amino Acid Sequences ◽  
Recent Advances ◽  
Cell Penetrating ◽  
A Cell ◽  
Low Toxicity ◽  
Applied Biology

Cell-penetrating-peptides (CPPs) are small amino-acid sequences characterized by their ability to cross cellular membranes. They can transport various bioactive cargos inside cells including nucleic acids, large proteins, and other chemical compounds. Since 1988, natural and synthetic CPPs have been developed for applications ranging from fundamental to applied biology (cell imaging, gene editing, therapeutics delivery). In recent years, a great number of studies reported the potential of CPPs as carriers for the treatment of various diseases. Apart from a good efficacy due to a rapid and potent delivery, a crucial advantage of CPP-based therapies is the peptides low toxicity compared to most drug carriers. On the other hand, they are quite unstable and lack specificity. Higher specificity can be obtained using a cell-specific CPP to transport the therapeutic agent or using a non-specific CPP to transport a cargo with a targeted activity. CPP-cargo complexes can also be conjugated to another moiety that brings cell- or tissue-specificity. Studies based on all these approaches are showing promising results. Here, we focus on recent advances in the potential usage of CPPs in the context of cancer therapy, with a particular interest in CPP-mediated delivery of anti-tumoral proteins.

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