Type II NADH dehydrogenase

A respiratory enzyme that bacteria need and we don't, and so a possible antibiotic target.

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Type II NADH dehydrogenase (NDH-2) feeds electrons into the respiratory chain of many bacteria, including pathogens, but humans and other mammals don’t have it. That makes it a promising target for new antibiotics. Working with Greg Cook and Yoshio Nakatani’s groups in New Zealand and Judy Hirst’s group in Cambridge, the structures from Caldalkalibacillus thermarum together with kinetics and mutagenesis showed that the enzyme handles its two substrates at separate sites, which resolved years of conflicting results about how it works (paper).

The crystals were small, diffracted weakly and suffered from radiation damage. Getting a usable dataset meant collecting with a microfocus beam from tens of crystals and picking the best wedges of data to merge.