Bisubstrate specificity in histidine/tryptophan biosynthesis isomerase from Mycobacterium tuberculosis by active site metamorphosis.

In histidine and tryptophan biosynthesis, two related isomerization reactions are generally catalyzed by two specific single-substrate enzymes (HisA and TrpF), sharing a similar (β/α)(8)-barrel scaffold. However, in some actinobacteria, one of the two encoding genes (trpF) is missing and the two reactions are instead catalyzed by one bisubstrate enzyme (PriA). To unravel the unknown mechanism of bisubstrate specificity, we used the Mycobacterium tuberculosis PriA enzyme as a model.

Extracellular superoxide dismutase exists as an octamer.

Human extracellular superoxide dismutase (EC-SOD) is involved in the defence against oxidative stress induced by the superoxide radical. The protein is a homotetramer stabilised by hydrophobic interactions within the N-terminal region. During the purification of EC-SOD from human aorta, we noticed that material with high affinity for heparin-Sepharose formed not only a tetramer but also an octamer.

The structure of rabbit extracellular superoxide dismutase differs from the human protein.

The cDNA sequence encoding rabbit, mouse, and rat extracellular superoxide dismutase (EC-SOD) predicts that the protein contains five cysteine residues. Human EC-SOD contains an additional cysteine residue and folds into two forms with distinct disulfide bridge patterns. One form is enzymatically active (aEC-SOD), while the other is inactive (iEC-SOD).