ETD Collection

Permanent URI for this collectionhttps://wiredspace.wits.ac.za/handle/10539/104


Please note: Digitised content is made available at the best possible quality range, taking into consideration file size and the condition of the original item. These restrictions may sometimes affect the quality of the final published item. For queries regarding content of ETD collection please contact IR specialists by email : IR specialists or Tel : 011 717 4652 / 1954

Follow the link below for important information about Electronic Theses and Dissertations (ETD)

Library Guide about ETD

Browse

Filters

2016 - 20183

Settings

Has files: YesSubject: search.filters.subject.Protein binding

Search Results

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    The biochemical functions of the Retinoblastoma binding protein 6 (RBBP 6) isoforms in metabolic reprogramming occurring during carcinogenesis
    (2018) Nsingwane, Zanele
    ABSTRACT The Retinoblastoma binding protein 6 is dysregulated in most cancers, indicating it may play a role in metabolic reprograming- a hallmark of carcinogenesis. Its human isoforms have been shown to play diverse roles in apoptosis. This study aimed to elucidate biochemical roles of RBBP6 isoforms in metabolic reprogramming during carcinogenesis. Drosophila melanogaster wild type and p53 null mutants were treated with drug permutations of irinotecan (DNA damaging agent) and exogenous pyruvate to perturb metabolism. Moreover, using RT-PCR and Western blot expression profiles of SNAMA (Drosophila Orthologue of RBBP6) isoforms were shown followed by survival studies to investigate the effects of these drugs. Furthermore, using bioinformatics the domains of RBBP6 isoforms in various species were shown. Results indicate that RBBP6 isoforms show contrasting expression patterns. Furthermore, exogenous pyruvate protects the wild type flies from irinotecan toxicity while killing p53 null mutants. RBBP6 proves to be a potential druggable target for chemotherapy.
  • No Thumbnail Available
    Item
    Drugs targeting the retinoblastoma binding protein 6 (RBBP6): "the collision of computers and biochemistry"
    (2017) Twala, Charmy Starnod
    Screening methodologies have identified specific targets that could serve as potential therapeutic markers in cancer drug design, and the Retinoblastoma binding protein 6 (RBBP6) which is predominately expressed in lung and breast cancers is one critical protein identified. This study seeks to understand the 3D structure of RBBP6 domains, with emphasis on cancer. Three of these domains have been studied in this project, i.e. the Domain With No Name (DWNN), RING Finger, and the p53-binding domain. The ubiquitin-like structure of the DWNN has implicated this domain as a ubiquitin-like modifier of other proteins such as p53, whilst the RING Finger domain has intrinsic E3 Ligase activity like MDM2 the prototypical negative regulator of p53. The DWNN and RING Finger domains have resolved solution NMR structures, whilst the p53-binding domain has none. Thus, the first initiative undertaken was to model the RBBP6 p53-binding domain using I-TASSER and eThread-Modeller web-severs. Our results demonstrated that this domain mainly constitutes of alpha-helices and loop structures. Structural quality validations of both I-TASSER and eThread-Modeller models were further assessed using Swiss-Model and ProSA (Protein structure analysis) web-servers. Analyses were focussed on specific statistical parameters (Anolea, DFire, QMEAN, ProCheck and the ProSA Z-score). Results from these analyses show that the first I-TASSER model is the best possible representation of the RBBP6 p53-binding domain depicting minimal deviation from native state. Furthermore, screening and docking studies were performed using Schrödinger-Maestro v10.7: Glide SP and drug-like molecules that would potentially serve as agonist or antagonist of RBBP6 were identified.
  • No Thumbnail Available
    Item
    Functional studies of the RBBP6 (retinoblastoma binding protein 6) gene and its related genes in breast and cervical cancer : a promising diagnostic and management assay for cancer progression
    (2016) Moela, Pontsho
    Overexpression of RBBP6 in cancers of the colon, lung and oesophagus makes it a potential target in anticancer therapy. This is especially important because it associates with the tumour suppressor gene p53, inactivation of which has been linked to over 50% of all cancer types. Cancer is an enormous burden of a disease globally. Today, more people die from cancer than HIV/AIDS, tuberculosis and malaria combined. And in females, breast and cervical malignancies remain the most common types. Currently, cervical cancer is the most diagnosed gynaecological cancer type, whose mortality rate is the highest in developing countries due to the asymptomatic nature of the disease coupled with inadequate cancer control tools and facilities. Breast cancer incidence rate has increased beyond that of lung cancer, making it the most common malignancy among women.