Cloning, expression and crystallization of dihydrodipicolinate reductase from methicillin-resistantStaphylococcus aureus Academic Article uri icon

abstract

  • Dihydrodipicolinate reductase (DHDPR; EC 1.3.1.26) catalyzes the nucleotide (NADH/NADPH) dependent second step of the lysine-biosynthesis pathway in bacteria and plants. Here, the cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of DHDPR from methicillin-resistant Staphylococcus aureus (MRSA-DHDPR) are presented. The enzyme was crystallized in a number of forms, predominantly with ammonium sulfate as a precipitant, with the best crystal form diffracting to beyond 3.65 A resolution. Crystal structures of the apo form as well as of cofactor (NADPH) bound and inhibitor (2,6-pyridinedicarboxylate) bound forms of MRSA-DHDPR will provide insight into the structure and function of this essential enzyme and valid drug target.

authors

  • Dommaraju, Sudhir
  • Gorman, Michael A
  • Dogovski, Con
  • Pearce, F Grant
  • Gerrard, Juliet A
  • Dobson, Renwick CJ
  • Parker, Michael W
  • Perugini, Matthew A

publication date

  • January 1, 2010