Objective
Phosphate ester hydrolysis is one of the most important classes of chemical reactions in biology, playing a central role in nucleic acid processing, energy transduction, and signalling. Despite the importance of this ubiquitous reaction, the mechanistic details of phosphate ester cleavage remain obscure due to the complex nature of the reaction. In addition, there is an active debate concerning possible reaction intermediates. Here we aim to clarify the molecular basis of this enzymatic mechanism by studying P-O bond cleavage by Nucleoside Triphosphate (NTP) - processing enzymes and by the HIV-RT system. Hydrolysis of NTP represents a biochemical reaction essential in most processes of life: energy storage and transfer, replication of the genetic material, translation, regulation, etc. We will clarify the roles of metal ions in NTP enzymes and the ubiquitous arginine finger-type interaction occurring during the catalytic process. Phosphate hydrolysis is also catalysed by the HIV-RT enzyme. HIV-RT is a main drug target for AIDS disease. Unfortunately, current HIV drugs cannot cure the disease, forcing patients to remain on viral suppressant medications indefinitely. The major emerging problem with the current HIV viral drugs is the acquired drug resistance. To combat this problem, it is essential to design new drugs that target alternative functions and binding sites. More than half of the current HIV drugs target the HIV-RT reverse transcriptase function. Nevertheless, HIV-RT also carries out an RNase H function that is essential to viral replication. Here, we aim to obtain detailed information on the conformational flexibility and tautomerism of the inhibitors and to find the link between these properties and the potency and selectivity of the RNase function inhibitors. By exploring the flexibility of the inhibitors as well as mutations in the protein, we also aim to identify how drug resistant mutants may emerge as a result of drug therapies.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules nucleic acids
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences chemical sciences
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-IEF
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
WC2R 2LS London
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.