INHIBITORS OF MESO-DAP AND LYSINE BIOSYNTHESIS: TARGETING DHDP SYNTHASE
Grant number: LX0776388
With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to treat a range of pathogenic bacteria, including "Golden Staph".
Related publications (4)
Crystallization and preliminary X-ray analysis of dihydrodipicolinate synthase from Clostridium botulinum in the presence of its substrate pyruvate
Sarah C Atkinson, Renwick CJ Dobson, Janet M Newman, Michael A Gorman, Con Dogovski, Michael W Parker, Matthew A Perugini
In this paper, the crystallization and preliminary X-ray diffraction analysis to near-atomic resolution of DHDPS from Clostridium ..
Irreversible inhibition of dihydrodipicolinate synthase by 4-oxo-heptenedioic acid analogues
Berin A Boughton, Michael DW Griffin, Paul A O'Donnell, Renwick CJ Dobson, Matthew A Perugini, Juliet A Gerrard, Craig A Hutton
We report the synthesis of (2E,5E)-4-oxoheptadienedioic acid and (2E)-4-oxoheptenedioic acid and evaluation of both diester and di..
Structure and evolution of a novel dimeric enzyme from a clinically important bacterial pathogen
Benjamin R Burgess, Renwick CJ Dobson, Michael F Bailey, Sarah C Atkinson, Michael DW Griffin, Geoffrey B Jameson, Michael W Parker, Juliet A Gerrard, Matthew A Perugini
Dihydrodipicolinate synthase (DHDPS) catalyzes the first committed step of the lysine biosynthetic pathway. The tetrameric structu..
Inhibiting dihydrodipicolinate synthase across species: Towards specificity for pathogens?
Voula Mitsakos, Renwick CJ Dobson, F Grant Pearce, Sean R Devenish, Genevieve L Evans, Benjamin R Burgess, Matthew A Perugini, Juliet A Gerrard, Craig A Hutton
Dihydrodipicolinate synthase (DHDPS) is a key enzyme in lysine biosynthesis and an important antibiotic target. The specificity of..