Abstract
Background: The Ribonuclease III (RNase III) enzymatic class is involved in many important biological processes from bacteria to higher eukaryotes. Consequently, they have been useful as drug-target candidates for drug development. Despite their high molecular diversity, RNases III share common structural and catalytic features and some degree of enzymatic activity. However, the role of accessory domains as key determinants of substrate selectivity and over the biological function of each RNase III type is still under study.
Results: The in vitro enzymatic activity of three RNase III members from class I (Escherichia coli RNase III, Schizosaccharomyces pombe Pac1 and Saccharomyces cerevisiae Rntp1) and the human Drosha placed in class II was revisited against four different substrates. These two RNase III classes comprise members showing different domain organization. Enzymatic activity differences were found among members of the class I, which were even higher when the human Drosha (class II) was tested. The substrate promiscuity of the E. coli RNase III was corroborated in vivo through its expression in S. cerevisiae, as reported previously, but was extended here to Pichia pastoris. The putative molecular mechanisms contributing for the lethal effect of the heterologous RNase III on the yeast lives were deeply discussed.
Conclusion: The new generated biochemical data integrated with previous available information affirmed that RNases III substrate specificity as well as their cellular biological role is highly influenced by its protein structure architecture. This fact also allowed drawing evolutionary links between RNase III members from their structural and substrate specificity differences.
Keywords: RNase III, Substrate specificity, Archetype, Lethal effect, E. coli, yeast.
Current Pharmaceutical Design
Title:How the Protein Architecture of RNases III Influences their Substrate Specificity?
Volume: 22 Issue: 33
Author(s): Guillermin Agüero-Chapin, Gisselle Pérez-Machado, Juan Collí Mull, Evys Ancede-Gallardo, Agostinho Antunes and Gustavo A. de la Riva de la Riva
Affiliation:
Keywords: RNase III, Substrate specificity, Archetype, Lethal effect, E. coli, yeast.
Abstract: Background: The Ribonuclease III (RNase III) enzymatic class is involved in many important biological processes from bacteria to higher eukaryotes. Consequently, they have been useful as drug-target candidates for drug development. Despite their high molecular diversity, RNases III share common structural and catalytic features and some degree of enzymatic activity. However, the role of accessory domains as key determinants of substrate selectivity and over the biological function of each RNase III type is still under study.
Results: The in vitro enzymatic activity of three RNase III members from class I (Escherichia coli RNase III, Schizosaccharomyces pombe Pac1 and Saccharomyces cerevisiae Rntp1) and the human Drosha placed in class II was revisited against four different substrates. These two RNase III classes comprise members showing different domain organization. Enzymatic activity differences were found among members of the class I, which were even higher when the human Drosha (class II) was tested. The substrate promiscuity of the E. coli RNase III was corroborated in vivo through its expression in S. cerevisiae, as reported previously, but was extended here to Pichia pastoris. The putative molecular mechanisms contributing for the lethal effect of the heterologous RNase III on the yeast lives were deeply discussed.
Conclusion: The new generated biochemical data integrated with previous available information affirmed that RNases III substrate specificity as well as their cellular biological role is highly influenced by its protein structure architecture. This fact also allowed drawing evolutionary links between RNase III members from their structural and substrate specificity differences.
Export Options
About this article
Cite this article as:
Agüero-Chapin Guillermin, Pérez-Machado Gisselle, Mull Collí Juan, Ancede-Gallardo Evys, Antunes Agostinho and Riva A. de la Riva de la Gustavo, How the Protein Architecture of RNases III Influences their Substrate Specificity?, Current Pharmaceutical Design 2016; 22 (33) . https://dx.doi.org/10.2174/1381612822666160511150416
DOI https://dx.doi.org/10.2174/1381612822666160511150416 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Targeting the p53-Family in Cancer and Chemosensitivity: Triple Threat
Current Drug Targets P2Y Receptors in the Mammalian Nervous System: Pharmacology, Ligands and Therapeutic Potential
CNS & Neurological Disorders - Drug Targets Mn-SOD and Chronic Inflammation of Gastric Mucosa
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry The Role of a Disturbed Arginine/NO Metabolism in the Onset of Cancer Cachexia: A Working Hypothesis
Current Medicinal Chemistry The Role of FTO in Tumors and Its Research Progress
Current Medicinal Chemistry Tropism-Modified Adenoviral and Adeno-Associated Viral Vectors for Gene Therapy
Current Gene Therapy DNA Copy Number Profiles Correlate with Outcome in Colorectal Cancer Patients Treated with Fluoropyrimidine/Antifolate-based Regimens
Current Drug Metabolism Body Composition and -174G/C Interleukin-6 Promoter Gene Polymorphism: Association with Progression of Insulin Resistance in Normal Weight Obese Syndrome
Current Pharmaceutical Design Colon Cancer Therapy: Recent Developments in Nanomedicine to Improve the Efficacy of Conventional Chemotherapeutic Drugs
Anti-Cancer Agents in Medicinal Chemistry Gene Delivery for Cancer Therapy
Current Drug Delivery Simultaneous Amplification of HER-2 (ERBB2) and Topoisomerase IIα (TOP2A) Genes - Molecular Basis for Combination Chemotherapy in Cancer
Current Cancer Drug Targets Patent Selections
Recent Patents on DNA & Gene Sequences New Cancer Chemotherapy Agents: Inhibitors of DNA Polymerase
Current Drug Therapy Inhibiting HSP90 to Treat Cancer: A Strategy in Evolution
Current Molecular Medicine Dynamic Localization of Hepatocellular Transporters: Role in Biliary Excretion and Impairment in Cholestasis
Current Medicinal Chemistry Proteinase-Activated Receptor 2 (PAR2): A Challenging New Target for Treatment of Vascular Diseases
Current Pharmaceutical Design Inhibition of Growth of Esophageal Cancer by Alantolactone via Wnt/β- Catenin Signaling
Anti-Cancer Agents in Medicinal Chemistry Editorial (Thematic Issue: Improving Cancer Clinical Research and Trials with Hispanic Populations: Training and Outreach Efforts Between Moffitt Cancer Center and the Ponce School of Medicine)
Reviews on Recent Clinical Trials COVID-19 Invades Several Important Organs other than the Lungs: Organs Crosstalk
Coronaviruses Editorial (Hot Topic Potential Value and Limitation of Dual Inhibitors of PI3K and mTOR in the Treatment of Cancer)
Current Cancer Drug Targets