scholarly journals Extracellular Ribonuclease fromBacillus licheniformis(Balifase), a New Member of the N1/T1 RNase Superfamily

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Yulia Sokurenko ◽  
Alsu Nadyrova ◽  
Vera Ulyanova ◽  
Olga Ilinskaya
Keyword(s):  
Unique Feature ◽  
Phosphate Starvation ◽  
Structural Similarity ◽  
Gene Organization ◽  
Chemotherapeutic Agents ◽  
Natural Conditions ◽  
Antitumor Effects ◽  
Calculated Molecular Weight ◽  
Its Gene ◽  
High Degree

The N1/T1 RNase superfamily comprises enzymes with well-established antitumor effects, such as ribotoxins secreted by fungi, primarily byAspergillusandPenicilliumspecies, and bacterial RNase secreted byB. pumilus(binase) andB. amyloliquefaciens(barnase). RNase is regarded as an alternative to classical chemotherapeutic agents due to its selective cytotoxicity towards tumor cells. New RNase with a high degree of structural similarity with binase (73%) and barnase (74%) was isolated and purified fromBacillus licheniformis(balifase, calculated molecular weight 12421.9 Da, pI 8.91). The protein sample with enzymatic activity of 1.5 × 106units/A280was obtained. The physicochemical properties of balifase are similar to those of barnase. However, in terms of its gene organization and promoter activity, balifase is closer to binase. The unique feature of balifase gene organization consists in the fact that genes of RNase and its inhibitor are located in one operon. Similarly to biosynthesis of binase, balifase synthesis is induced under phosphate starvation; however, in contrast to binase, balifase does not form dimers under natural conditions. We propose that the highest stability of balifase among analyzed RNase types allows the protein to retain its structure without oligomerization.

Probiotics for the Chemoprotective Role Against the Toxic Effect of Cancer Chemotherapy

2021 ◽  
Vol 21 ◽  
Author(s):  
Aafrin Waziri ◽  
Charu Bharti ◽  
Mohammed Aslam ◽  
Parween Jamil ◽  
Aamir Mirza ◽  
...  
Keyword(s):  
Side Effects ◽  
Clinical Management ◽  
Clinical Evidence ◽  
Unmet Need ◽  
Chemotherapeutic Agents ◽  
Antitumor Effects ◽  
Anti Cancer ◽  
Different Types ◽  
Growth Promoting ◽  
High Degree

Background: The processes of chemo- and radiation therapy-based clinical management of different types of cancers are associated with toxicity and side effects of chemotherapeutic agents. So, there is always an unmet need to explore agents to reduce such risk factors. Among these, natural products have generated much attention because of their potent antioxidant and antitumor effects. In the past, some breakthrough outcomes established that various bacteria in the human intestinal gut are bearing growth-promoting attributes and suppressing the conversion of pro-carcinogens into carcinogens. Hence, probiotics integrated approaches are nowadays being explored as rationalized therapeutics in the clinical management of cancer. Methods: Here, published literature was explored to review chemoprotective roles of probiotics against toxic and side effects of chemotherapeutics. Results: Apart from excellent anti-cancer abilities, probiotics are bearing and alleviate toxicity and side effects of chemotherapeutics, with a high degree of safety and efficiency. Conclusion: Preclinical and clinical evidence suggested that due to the chemoprotective roles of probiotics against side effects and toxicity of chemotherapeutics, their integration in chemotherapy would be a judicious approach.

scholarly journals Gold (III) Derivatives in Colon Cancer Treatment

2022 ◽  
Vol 23 (2) ◽  
pp. 724
Author(s):  
Agata Gurba ◽  
Przemysław Taciak ◽  
Mariusz Sacharczuk ◽  
Izabela Młynarczuk-Biały ◽  
Magdalena Bujalska-Zadrożny ◽  
...  
Keyword(s):  
Protein Structures ◽  
Thioredoxin Reductase ◽  
Structural Similarity ◽  
In Vivo Studies ◽  
Antitumor Effects ◽  
Solubility In Water ◽  
Physiological Conditions ◽  
Drug Candidates ◽  
New Methods

Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.

Data Integration Through Protein Ontology

2011 ◽  
pp. 106-122
Author(s):  
Amandeep S. Sidhu ◽  
Tharam S. Dillon ◽  
Elizabeth Chang
Keyword(s):  
Hierarchical Classification ◽  
Structural Similarity ◽  
Protein Annotation ◽  
Functional Identification ◽  
Sequence Identity ◽  
Alternative Protein ◽  
Traditional Approaches ◽  
High Degree ◽  
Keyword Searches

Traditional approaches to integrate protein data generally involved keyword searches, which immediately excludes unannotated or poorly annotated data. An alternative protein annotation approach is to rely on sequence identity, or structural similarity, or functional identification. Some proteins have high degree of sequence identity, or structural similarity, or similarity in functions that are unique to members of that family alone. Consequently, this approach can’t be generalized to integrate the protein data. Clearly, these traditional approaches have limitations in capturing and integrating data for Protein Annotation. For these reasons, we have adopted an alternative method that does not rely on keywords or similarity metrics, but instead uses ontology. In this chapter we discuss conceptual framework of Protein Ontology that has a hierarchical classification of concepts represented as classes, from general to specific; a list of attributes related to each concept, for each class; a set of relations between classes to link concepts in ontology in more complicated ways then implied by the hierarchy, to promote reuse of concepts in the ontology; and a set of algebraic operators for querying protein ontology instances.

Subunit δ of Chloroplast F0F1 ATPase and OSCP of Mitochondrial F0F1 ATPase: a Comparison by CD-Spectroscopy

1991 ◽  
Vol 46 (9-10) ◽  
pp. 759-764 ◽  
Author(s):  
Siegfried Engelbrecht ◽  
Jennifer Reed ◽  
François Penin ◽  
Danièle C. Gautheron ◽  
Wolfgang Junge
Keyword(s):  
Primary Structure ◽  
Tertiary Structure ◽  
Atp Synthesis ◽  
Structural Similarity ◽  
Cd Spectroscopy ◽  
Α Helix ◽  
And Function ◽  
High Degree ◽  
Very High ◽  
Secondary And Tertiary Structure

Abstract CD spectra have been recorded with subunit δ from chloroplast CF0CF1 and with OSCP from mitochondrial MF0MF1. These subunits are supposed to act similarly at the interface between proton transport through the F0-portion and ATP-synthesis in the F1-portion of their respective F0F1-ATPase. Evaluation of the data for both proteins revealed a very high α-helix content of -85% and practically no β-sheets. Despite their low homology on the primary structure level (23% identity) and their different electrostatic properties (pl-values differ by 3 units), spinach δ and porcine OSCP are indistinguishable with respect to their secondary structure as measured by CD. Prediction and analysis of consensual a-helices even in poorly conserved regions indicate α high degree of structural similarity between chloroplast δ and OSCP. In view of the topology and function of δ and OSCP in intact F0F1 these findings are interpreted to indicate the dominance of secondary and tertiary structure over the primary structure in their supposed function between proton flow and ATP-synthesis.

scholarly journals A Key Motif in the Cholesterol-Dependent Cytolysins Reveals a Large Family of Related Proteins

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Jordan C. Evans ◽  
Bronte A. Johnstone ◽  
Sara L. Lawrence ◽  
Craig J. Morton ◽  
Michelle P. Christie ◽  
...  
Keyword(s):  
Large Family ◽  
Structural Similarity ◽  
Particle Analysis ◽  
Critical Component ◽  
Content Type ◽  
Conserved Motif ◽  
Forming Mechanism ◽  
Terrestrial Environments ◽  
Pore Complexes ◽  
High Degree

ABSTRACT The cholesterol-dependent cytolysins (CDCs) are bacterial, β-barrel, pore-forming toxins. A central enigma of the pore-forming mechanism is how completion of the prepore is sensed to initiate its conversion to the pore. We identified a motif that is conserved between the CDCs and a diverse family of nearly 300 uncharacterized proteins present in over 220 species that span at least 10 bacterial and 2 eukaryotic phyla. Except for this motif, these proteins exhibit little similarity to the CDCs at the primary structure level. Studies herein show this motif is a critical component of the sensor that initiates the prepore-to-pore transition in the CDCs. We further show by crystallography, single particle analysis, and biochemical studies of one of these CDC-like (CDCL) proteins from Elizabethkingia anophelis, a commensal of the malarial mosquito midgut, that a high degree of structural similarity exists between the CDC and CDCL monomer structures and both form large oligomeric pore complexes. Furthermore, the conserved motif in the E. anophelis CDCL crystal structure occupies a nearly identical position and makes similar contacts to those observed in the structure of the archetype CDC, perfringolysin O (PFO). This suggests a common function in the CDCs and CDCLs and may explain why only this motif is conserved in the CDCLs. Hence, these studies identify a critical component of the sensor involved in initiating the prepore-to-pore transition in the CDCs, which is conserved in a large and diverse group of distant relatives of the CDCs. IMPORTANCE The cholesterol-dependent cytolysins’ pore-forming mechanism relies on the ability to sense the completion of the oligomeric prepore structure and initiate the insertion of the β-barrel pore from the assembled prepore structure. These studies show that a conserved motif is an important component of the sensor that triggers the prepore-to-pore transition and that it is conserved in a large family of previously unidentified CDC-like proteins, the genes for which are present in a vast array of microbial species that span most terrestrial environments, as well as most animal and human microbiomes. These studies establish the foundation for future investigations that will probe the contribution of this large family of CDC-like proteins to microbial survival and human disease.

scholarly journals Characterization of the Nucleolar Gene Product, Treacle, in Treacher Collins Syndrome

2000 ◽  
Vol 11 (9) ◽  
pp. 3061-3071 ◽  
Author(s):  
Cynthia Isaac ◽  
Karen L. Marsh ◽  
William A. Paznekas ◽  
Jill Dixon ◽  
Michael J. Dixon ◽  
...  
Keyword(s):  
Gene Product ◽  
Full Length ◽  
Treacher Collins Syndrome ◽  
Autosomal Dominant Disorder ◽  
Premature Termination Codons ◽  
Its Gene ◽  
Repeat Domain ◽  
Primary Fibroblasts ◽  
Single Allele ◽  
High Degree

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development caused by mutations in the geneTCOF1. Its gene product, treacle, consists mainly of a central repeat domain, which shows it to be structurally related to the nucleolar phosphoprotein Nopp140. Treacle remains mostly uncharacterized to date. Herein we show that it, like Nopp140, is a highly phosphorylated nucleolar protein. However, treacle fails to colocalize with Nopp140 to Cajal (coiled) bodies. As in the case of Nopp140, casein kinase 2 appears to be responsible for the unusually high degree of phosphorylation as evidenced by its coimmunoprecipitation with treacle. Based on these and other observations, treacle and Nopp140 exhibit distinct but overlapping functions. The majority of TCOF1 mutations in TCS lead to premature termination codons that could affect the cellular levels of the full-length treacle. We demonstrate however, that the cellular amount of treacle varies less than twofold among a collection of primary fibroblasts and lymphoblasts and regardless of whether the cells were derived from TCS patients or healthy individuals. Therefore, cells of TCS patients possess a mechanism to maintain wild-type levels of full-length treacle from a single allele.

Roles of aggrecan domains in biosynthesis, modification by glycosaminoglycans and product secretion

2001 ◽  
Vol 354 (1) ◽  
pp. 199-207 ◽  
Author(s):  
Chris KIANI ◽  
Vivian LEE ◽  
Liu CAO ◽  
Liwen CHEN ◽  
Yaojiong WU ◽  
...  
Keyword(s):  
Tandem Repeats ◽  
Unique Feature ◽  
Chondroitin Sulphate ◽  
Attachment Site ◽  
Structural Similarity ◽  
Globular Domain ◽  
Keratan Sulphate ◽  
Central Sequence ◽  
Domain Sequence ◽  
C Terminus

Aggrecan is a member of the chondroitin sulphate (CS) proteoglycan family, which also includes versican/PG-M, neurocan and brevican. Members of this family exhibit structural similarity: a G1 domain at the N-terminus and a G3 domain at the C-terminus, with a central sequence for modification by CS chains. A unique feature of aggrecan is the insertion of three additional domains, an inter-globular domain (IGD), a G2 domain and a keratan sulphate (KS) domain (sequence modified by KS chains), between the G1 domain and the CS domain (sequence modified by CS chains). The G1 and G3 domains have been implicated in product secretion, but G2, although structurally similar to the tandem repeats of G1, performs an unknown function. To define the functions of each aggrecan domain in product processing, we cloned and expressed these domains in various combinations in COS-7 cells. The results indicated that the G3 domain enhanced product secretion, alone or in combination with the KS or CS domain, and promoted glycosaminoglycan (GAG) chain attachment. Constructs containing the G1 domain were not secreted. Addition of a CS domain sequence to G1 reduced this inhibition, but GAG chain attachment was still decreased. The potential GAG chain attachment site in the IGD was occupied by GAGs, and IGD product was secreted efficiently. The KS domain was modified by GAG chains and secreted. Finally, the G2 domain was expressed but not secreted, and inhibited secretion of the IGD when expressed as an IGD–G2 combination.

scholarly journals Cardiovascular Oncologic Emergencies

Cardiology ◽  
2017 ◽  
Vol 138 (3) ◽  
pp. 147-158 ◽  
Author(s):  
Sundeep Shenoy ◽  
Safal Shetty ◽  
Shilpa Lankala ◽  
Faiz Anwer ◽  
Andrew Yeager ◽  
...  
Keyword(s):  
Superior Vena Cava Syndrome ◽  
Superior Vena ◽  
Vena Cava ◽  
Cardiovascular Complications ◽  
Pericardial Tamponade ◽  
Chemotherapeutic Agents ◽  
Oncologic Emergencies ◽  
Vena Cava Syndrome ◽  
High Degree ◽  
Very High

Oncologic emergencies can present either as a progression of a known cancer or as the initial presentation of a previously undiagnosed cancer. In most of these situations, a very high degree of suspicion is required to allow prompt assessment, diagnosis, and treatment. In this article, we review the presentation and management of cardiovascular oncologic emergencies from primary and metastatic tumors of the heart and complications such as pericardial tamponade, superior vena cava syndrome, and hyperviscosity syndrome. We have included the cardiovascular complications from radiation therapy, chemotherapeutic agents, and biologic agents used in modern cancer treatment.

Celastrol Overcomes Chemoresistance in Vitro and Potentiates the Effect of Bortezomib Against Human Multiple Myeloma in Nude Mice Mode

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5017-5017
Author(s):  
Radhamani Kannaiyan ◽  
Manu Kanjoormana Aryan ◽  
Muthu K Shanmugam ◽  
Feng Li ◽  
Gautam Sethi
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Cell Lines ◽  
Nude Mice ◽  
Tumor Volume ◽  
Corn Oil ◽  
Conflicts Of Interest ◽  
Chemotherapeutic Agents ◽  
Antitumor Effects ◽  
Group I

Abstract Abstract 5017 Introduction: Multiple myeloma (MM) is a B cell malignancy characterized by clonal proliferation of B cell in the bone marrow with low proliferative index. Despite the advent of novel therapeutics in addition to conventional chemotherapeutics, MM remains incurable because of the development of chemoresistance. Persistent activation of NF-κB/STAT3 signaling pathways and deregulation of apoptosis is considered to play an important role in the development of chemoresistance. The use of anticancer drugs derived from natural sources may be able to overcome resistance without some of the debilitating side effects of conventional chemotherapy. Celastrol is one such compound that has gained substantial attention recently for its anti-inflammatory and anticancer activities and is derived from the Chinese medicinal plant ‘Tripterygium wilfordii. We have demonstrated that celastrol overcomes the chemoresistance and induce apoptosis in MM cells by inhibiting NF-κB and STAT 3 pathways cell lines sensitive and resistant to various chemotherapeutic agents and Bortezomib. Our experimental findings have indicated that celastrol in combination with bortezomib/thalidomide can inhibit proliferation, induce apoptosis and overcome chemoresistance in MM cells in synergistic manner. We also observed that celastrol inhibited the activation of NF-κB and STAT3 and downregulated the expression of various genes involved in MM proliferation, survival and angiogenesis. Materials and Methods: Male athymic balb/c nude mice were implanted with 2×106 cells with either Human MM U266 cell lines subcutaneously. When tumors have reached more than 0. 3 cm in diameter, the mice were randomized into four groups. Group I (control) received corn oil 100 ul i. p. for five days a week, group II received 0. 25 mg/kg celastrol in 100ul corn oil for five days a week, group III received 0. 25 mg/kg bortezomib in 100 ul corn oil i. p. weekly and group IV received 0. 25mg/kg celastrol in 100 ul corn oil i. p. 5 days a week and 0. 25 mg/kg bortezomib in 100 ul corn oil i. p. weekly for 3 consecutive weeks. The tumor volume and body weight of the mice were monitored twice a week for the duration of the experiment. On completion of the treatment period, mice were euthanized by i. p. phentobarbital (40 mg/kg b. w) followed by cervical dislocation and then tumors were dissected and diameters measured. The tumor volume was calculated using the formula [L × W2]/2, where W and L are the width (short diameter) and the length (long diameter) of the tumor and the tumors were subjected to histological examination. Results: In the MM xenograft mice model, we observed that celastrol potentiated the antitumor effects of bortezomib and this correlated with significant suppression of NF-κB, STAT3, COX-2 and VEGF which was demonstrated by IHC. Overall, our data indicates that celastrol could be a potential therapeutic agent for the treatment of MM, especially in combination with the novel anti-myeloma agents. Disclosures: No relevant conflicts of interest to declare.

Use of the Microculture Kinetic Assay of Apoptosis to Determine Chemosensitivities of Leukemias

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 968-980
Author(s):  
Vladimir D. Kravtsov ◽  
John P. Greer ◽  
James A. Whitlock ◽  
Mark J. Koury
Keyword(s):  
Cell Lines ◽  
Leukemia Cell ◽  
Chemotherapeutic Agents ◽  
Leukemia Cells ◽  
Target Cells ◽  
Apoptotic Cells ◽  
Chemosensitivity Test ◽  
Antitumor Effects ◽  
Kinetic Assay ◽  
Specific Patient

Chemotherapeutic agents exert their antitumor effects by inducing apoptosis. The microculture kinetic (MiCK) assay provides an automated, continuous means of monitoring apoptosis in a cell population. We used the MiCK assay to determine the chemosensitivities of the human promyelocytic HL-60 and lymphoblastic CEM cell lines and leukemia cells freshly isolated from patients with acute nonlymphocytic (ANLL) or acute lymphocytic (ALL) leukemias. Continuous monitoring of apoptosis in the MiCK assay permits determination of the time to the maximum apoptosis (Tm) and its two components which are initiation time (Ti) and development time (Td). Duration of the three timing components of apoptosis varies from hours to days depending on the drug, drug concentration, and type of target cells. In the MiCK assay, the extent of apoptosis is reported in kinetic units of apoptosis. Kinetic units are determined by the slope of the curve created when optical density caused by cell blebbing is plotted as a function of time. Using the leukemia cell lines, we define the relationship between kinetic units determined by the MiCK assay and the percentage of morphologically apoptotic cells in the culture. Flow cytometry analysis of apoptosis in Annexin-V-fluorescein isothiocyanate–labeled preparations of HL-60 and CEM cells was also used to compare with data obtained by the MiCK assay. The feasibility of the MiCK assay of apoptosis as a chemosensitivity test was confirmed by its comparison with a 3H-thymidine incorporation assay. We show that samples from 10 ANLL and ALL patients patients tested for sensitivity to various doses of idarubicin (IDR), daunorubicin (DNR), or mitoxantrone (MTA) gave the same percentages of apoptotic cells when calculated by the MiCK assay as when determined by morphological analysis. The MiCK assay was used for dose-response analyses of the sensitivities to IDR, DNR, and MTA of leukemia cells from 4 other patients (2 ANLL and 2 ALL). The results from both cell lines and patient samples indicate that ANLL cells are more sensitive than ALL cells to all three of these chemotherapeutic agents. However, for individual patients the chemosensitivities varied significantly among the three chemotherapeutic agents. These varying responses to IDR, DNR, and MTA indicate that the MiCK assay results can be of potential use in designing a treatment regimen for a specific patient with acute leukemia. Among several drugs of presumed similar efficacy, the MiCK assay can permit the selection of the specific chemotherapeutic agent that causes the most apoptosis in the patient's leukemic cells. © 1998 by The American Society of Hematology.

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