Unravelling structure and mechanism of adenine(22)-tRNA methyltransferase: towards novel antibiotics against MRSA (360G-Wellcome-208980_Z_17_Z)

£99,930

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital infections worldwide. Once restricted to healthcare facilities, this bacterium has now been found to cause infections in otherwise healthy communities. MRSA isolates have emerged that are resistant to most antibiotics in clinical use. It is imperative that new drugs be developed against MRSA. It is easier to develop specific antibiotics when the bacterial molecules they are meant to target are well understood. Enzymes accelerate chemical reactions in all living beings. If we produce a drug that inhibits an enzyme essential for MRSA growth, that drug will stop infections. If such enzyme is absent in humans, a specific drug can be developed to avoid side effects. The enzyme N1-adenine(22)-tRNA methyltransferase (TrmK) is essential in MRSA and absent in humans, fitting the aforementioned criteria. However, we know little about its structure and function. In this project, we will elucidate the mechanism of action of TrmK using enzyme kinetics and crystallography. Our results will pave the way for follow-up work aiming at rational design of specific inhibitors to be further developed into drugs against MRSA infection. Keywords: kinetics, enzyme mechanism, crystal structure, tRNA methyltransferase, antibiotics

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Grant Details

Amount Awarded 99930
Applicant Surname da Silva
Approval Committee Science Seeds Advisory Panel
Award Date 2017-09-05T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Seed Award in Science
Internal ID 208980/Z/17/Z
Lead Applicant Dr Rafael da Silva
Partnership Value 99930
Planned Dates: End Date 2021-06-30T00:00:00+00:00
Planned Dates: Start Date 2018-05-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland