20 Works

SELENOPROTEIN K

Polo, Andrea; Guariniello, Stefano; Colonna, Giovanni; Ciliberto, Gennaro; Costantini, Susan
SELK is a single-pass trans-membrane protein that resides in the endoplasmic reticulum membrane (ER) with a C-terminal domain exposed to the cytoplasm that is known to interact with different components of the endoplasmic reticulum associated to the protein degradation (ERAD) pathway. This protein is resulted to be up-expressed in hepatocellular carcinoma and in other cancers, therefore there is a need to analyze its structure-function relationships. In this work we performed a detailed analysis of the...

Full Length 3D Monomer Structure of Human Tumor Suppressor Protein p53 Using Homology Based Approach Combined with a Refinement process

Raghavan, Vaijayanthi; Agrahari, Maulishree; Dhankale, Dhananjaya Kalegowda
p53 is a very important Tumor Suppressor Protein that plays key roles in many cellular mechanisms thus preventing the development of cancers in humans. Its gene, TP53 is positioned on chromosome 17p13 and encodes a 53 kilodalton nucleophosphoprotein which is a transcription factor with a central role in cell cycle regulation. However, mutations in this protein lead to various types of human cancers and it is estimated that more than 50% of human cancers are...

NS3 MutantL (JFH-1)

Yennamalli, Ragothaman M; Veerapu, Naga Suresh
To gain an insight into mutation flexibility across sequence space of hepatitis C virus (HCV) genome, we created mutant libraries, differing from the parent sequence as well as each other by using a random mutagenesis approach; the proportion of mutations increased across these libraries with declining template amount or dATP concentration. Replication efficiency of full-genome mutant libraries ranged between 71 and 329 foci forming unit (FFU) per 105 Huh7.5 cells. Mutant libraries with low proportions...

NS3 MutantM (JFH-1)

Yennamalli, Ragothaman M; Veerapu, Naga Suresh
To gain an insight into mutation flexibility across sequence space of hepatitis C virus (HCV) genome, we created mutant libraries, differing from the parent sequence as well as each other by using a random mutagenesis approach; the proportion of mutations increased across these libraries with declining template amount or dATP concentration. Replication efficiency of full-genome mutant libraries ranged between 71 and 329 foci forming unit (FFU) per 105 Huh7.5 cells. Mutant libraries with low proportions...

NS3 MutantH (JFH-1)

Yennamalli, Ragothaman M; Veerapu, Naga Suresh
To gain an insight into mutation flexibility across sequence space of hepatitis C virus (HCV) genome, we created mutant libraries, differing from the parent sequence as well as each other by using a random mutagenesis approach; the proportion of mutations increased across these libraries with declining template amount or dATP concentration. Replication efficiency of full-genome mutant libraries ranged between 71 and 329 foci forming unit (FFU) per 105 Huh7.5 cells. Mutant libraries with low proportions...

Selenophosphate Synthetase 2 (SEPHS2)

Nunziata, Carmine; Polo, Andrea; Sorice, Angela; Budillon, Alfredo; Costantini, Susan
Selenophosphate synthetase 2 (SEPHS2) synthesizes from selenide and ATP the selenophosphate that represents the selenium donor used to synthesize selenocysteine (Sec), which is co-translationally incorporated into the selenoproteins. Only few information are reported in literature about SEPHS2 involvement in cancer. Thus, it should be interesting to understand what is its functional role in cancer development and progression. In this work, since up to now no structure was experimentally determined for SEPHS2, we decided to analyze...

Formyl peptide receptor 1 (FPR1)

Polo, Andrea; Ciliberto, Gennaro; Budillon, Alfredo; Costantini, Susan; Carriero, Maria Vincenza
Formyl peptide receptor 1 (FPR1) is a cell surface receptor protein, belonging to G protein-coupled receptor (GPCR) super-family, that binds and is activated by oligopeptides containing the N-Formylmethionine which are released by microorganisms and injured tissues. Hence, FPR1 is an important component of the immune system operating on host defense and inflammation. It is known that its high expression in several cancers although its function in tumor invasion and metastasis is poorly known. In this...

Structural insight on ATP hydrolysis in RecA/triple-stranded DNA nucleofilament

Chantal Prévost
Homologous recombination (HR) is a fundamental process that allows the faithful repair of DNA double strand breaks through the exchange of DNA strands between homologous regions of the genome. In bacteria, the exchange takes place within nucleofilaments of the RecA protein formed on a DNA strand from the damaged region. ATP is hydrolyzed in large quantity during the HR process, yet how exactly hydrolysis influences the DNA strand exchange reaction at the structural level remains...

Herbaspirillum seropedicae Recombinase A, active form, L53Q mutant

Penteado, Renato Ferras; Iulek, Jorge
In this work we have performed in vitro, in vivo and in silico studies of Recombinase A from Herbaspirillum seropedicae (HsRecA) - Uniprot AC Q9F672 -, both the wild type and the L53Q mutant. This mutation is located at the Make ATP Work motif (MAW) and impairs the ATPase and DNA-strand exchange activities, however, it does not affect the binding of ADP, ATP and ssDNA. At complementation studies of E. coli recA1 with the HsRecA...

Model of the VSV L terminal initiation complex

Green, Todd J; Ogino, Tomoaki; Ogino, Minako; Gupta, Nirmala
A homology-based model of the VSV L terminal initiation complex was generated based on the bacteriophage Φ6 initiation complex. RNA was modeled based on alignment of the core polymerases of VSV (PDB id: 5A22) and bacteriophage Φ6 (PDB id: 1HI0).

Arabidopsis DXO1 links RNA turnover and chloroplast function independently of its enzymatic activity

Kwaśnik, Aleksandra; Kufel, Joanna
The DXO family of proteins participates in eukaryotic mRNA 5′-end quality control, removal of non-canonical NAD+ cap and maturation of fungal rRNA precursors. In this work, we characterize the Arabidopsis thaliana DXO homolog, DXO1. We demonstrate that the plant-specific modification within the active site negatively affects 5′-end capping surveillance properties of DXO1, but has only a minor impact on its strong deNADding activity. Unexpectedly, catalytic activity does not contribute to striking morphological and molecular aberrations...

Multidrug transporter MexY of Pseudomonas aeruginosa

Ramaswamy, Venkata Krishnan; Vargiu, Attilio Vittorio; Malloci, Giuliano; Dreier, Jürg; Ruggerone, Paolo
Secondary multidrug transporters of the resistance-nodulation-cell division (RND) superfamily contribute crucially to antibiotic resistance in Gram-negative bacteria. Compared to the most studied transporter AcrB of E. coli, little is known about the molecular determinants of distinct polyspecificities of the most important RND transporters MexB and MexY of Pseudomonas aeruginosa. The absence of an experimental structure of MexY and the availability of only one structure of MexB bound to compounds (the ABI-PP inhibitor D13-9001) have made...

Herbaspirillum seropedicae Recombinase A, active form, wild type

Penteado, Renato Ferras; Iulek, Jorge
In this work we have performed in vitro, in vivo and in silico studies of Recombinase A from Herbaspirillum seropedicae (HsRecA) - Uniprot AC Q9F672 -, both the wild type and the L53Q mutant. This mutation is located at the Make ATP Work motif (MAW) and impairs the ATPase and DNA-strand exchange activities, however, it does not affect the binding of ADP, ATP and ssDNA. At complementation studies of E. coli recA1 with the HsRecA...

Arsenate Reductase (ArsC) of Deinococcus indicus DR1

Chauhan, Deepika; Srivastava, Pulkit Anupam; Agnihotri, Vidushi; Yennamalli, Ragothaman M; Priyadarshini, Richa
Tolerance to Arsenic, either as the pentavalent [As(V)] form or the trivalent form [As(III)], by bacteria has been well studied in prokaryotes and the mechanism of action is well defined. However, in the rod-shaped highly arsenic tolerant Deinococcus indicus the key enzyme, arsenate reductase (ArsC) has not been well studied. While it shares homology with the well-studied ArsC of E.coli, we report that the mechanism of action of As(V) is different and most likely due...

GmsPLA2-XIA-I

Maria Elisa Mariani
In silico and in vitro characterization of phospholipase A2 isoforms from soybean (Glycine max) At the present, no secreted phospholipase A2 (sPLA2) from soybean (Glycine max) was investigated in detail. In this work we identified five sequences of putative secreted sPLA2 from soybean after a BLAST search in G. max database. Sequence analysis showed a conserved PA2c domain bearing the Ca2þ binding loop and the active site motif. All the five mature proteins contain 12...

Structural insight on ATP hydrolysis in RecA/dsDNA nucleofilament

Prévost, Chantal; Boyer, Benjamin; Danilowicz, Claudia; Prentiss, Mara
Homologous recombination (HR) is a fundamental process that allows the faithful repair of DNA double strand breaks through the exchange of DNA strands between homologous regions of the genome. In bacteria, the exchange takes place within nucleofilaments of the RecA protein formed on a DNA strand from the damaged region. ATP is hydrolyzed in large quantity during the HR process, yet how exactly hydrolysis influences the DNA strand exchange reaction at the structural level remains...

Structural insight on ATP hydrolysis in RecA/ssDNA nucleofilament

Prévost, Chantal; Boyer, Benjamin; Danilowicz, Claudia; Prentiss, Mara
Homologous recombination (HR) is a fundamental process that allows the faithful repair of DNA double strand breaks through the exchange of DNA strands between homologous regions of the genome. In bacteria, the exchange takes place within nucleofilaments of the RecA protein formed on a DNA strand from the damaged region. ATP is hydrolyzed in large quantity during the HR process, yet how exactly hydrolysis influences the DNA strand exchange reaction at the structural level remains...

Theoretical model of complex between phosphoglycerate kinase 1 and DJ1

Bilsland, Alan; Boyd, Susan; Turnbull, Andrew; Jenkinson, David; Roffey, Jon; Keith, W. Nicol
Telomere signalling and metabolic dysfunction are hallmarks of cell aging, and are associated with a variety of pathologies. Identification of new agents targeting these processes might provide therapeutic opportunities, including chemoprevention strategies against cancer predisposition. Here we report identification and characterization of a pyrazolopyrimidine compound series that emerged from screens focused on cell immortality pathways and whose targets are glycolytic kinase PGK1 and oxidative stress sensor DJ1. We initially performed structure-activity studies on the series...

Oxytocin GKR

Bogdan A Danalache
Oxytocin-Gly-Lys-Arg: A Novel Cardiomyogenic Peptide BACKGROUND: Oxytocin (OT), synthesized in the heart, has the ability to heal injured hearts and to promote cardiomyogenesis from stem cells. Recently, we reported that the OT-GKR molecule, a processing intermediate of OT, potently increased the spontaneous formation of cardiomyocytes (CM) in embryonic stem D3 cells and augmented glucose uptake in newborn rat CM above the level stimulated by OT. In the present experiments, we investigated whether OT-GKR exists in...

Structure of Prototypic Peptide Transporter DtpA from E. coli in Complex with Valganciclovir Provides Insights into Drug Binding of Human PepT1

Rantos, Vasileios; Kosinski, Jan; Loew, Christian; Ural-Blimke, Yonca
Members of the solute carrier 15 family (SLC15) transport di- and tripeptides as well as peptidomimetic drugs across the cell membrane. Structures of bacterial homologues have provided valuable information on the binding and transport of their natural substrates, but many do not transport medically relevant drugs. In contrast, a homologue from Escherichia coli, DtpA, shows a high similarity to human PepT1 (SLC15A1) in terms of ligand selectivity and transports a similar set of drugs. Here,...

Registration Year

  • 2019
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Resource Types

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