Structure of the manganese superoxide dismutase from Deinococcus radiodurans in two crystal forms.

The structure of the manganese superoxide dismutase (Mn-SOD; DR1279) from Deinococcus radiodurans has been determined in two different crystal forms. Both crystal forms are monoclinic with space group P2(1). Form I has unit-cell parameters a = 44.28, b = 83.21, c = 59.52 angstroms, beta = 110.18 degrees and contains a homodimer in the asymmetric unit, with structure refinement (R = 16.8%, R(free) = 23.6%) carried out using data to d(min) = 2.2 angstroms. Form II has unit-cell parameters a = 43.57, b = 87.10, c = 116.42 angstroms, beta = 92.1 degrees and an asymmetric unit containing two Mn-SOD homodimers; structure refinement was effected to a resolution of 2.0 angstroms (R = 17.2%, R(free) = 22.3%). The resulting structures are compared with that of Mn-SOD from Escherichia coli, with which they are shown to be essentially isostructural.

Structural basis of 5-nitroimidazole antibiotic resistance: the crystal structure of NimA from Deinococcus radiodurans.

5-Nitroimidazole-based antibiotics are compounds extensively used for treating infections in humans and animals caused by several important pathogens. They are administered as prodrugs, and their activation depends upon an anaerobic 1-electron reduction of the nitro group by a reduction pathway in the cells. Bacterial resistance toward these drugs is thought to be caused by decreased drug uptake and/or an altered reduction efficiency. One class of resistant strains, identified in Bacteroides, has been shown to carry Nim genes (NimA, -B, -C, -D, and -E), which encode for reductases that convert the nitro group on the antibiotic into a non-bactericidal amine. In this paper, we have described the crystal structure of NimA from Deinococcus radiodurans (drNimA) at 1.6 A resolution. We have shown that drNimA is a homodimer in which each monomer adopts a beta-barrel fold. We have identified the catalytically important His-71 along with the cofactor pyruvate and antibiotic binding sites, all of which are found at the monomer-monomer interface. We have reported three additional crystal structures of drNimA, one in which the antibiotic metronidazole is bound to the protein, one with pyruvate covalently bound to His-71, and one with lactate covalently bound to His-71. Based on these structures, a reaction mechanism has been proposed in which the 2-electron reduction of the antibiotic prevents accumulation of the toxic nitro radical. This mechanism suggests that Nim proteins form a new class of reductases, conferring resistance against 5-nitroimidazole-based antibiotics.