Download citation
Acta Cryst. (2014). A70, C821
Download citation

link to html
Trichomoniasis is a common STD with an estimated prevalence of 4 million infections in the United States. The organism that causes trichomoniasis, Trichomonas vaginalis, is essentially anaerobic and contains proteins such as peroxidases that help detoxify reactive oxygen species in its environment. A unique non-heme peroxidase called rubrerythrin, found in this organism, is homologous to bacterial peroxidases, and is markedly upregulated during oxidative stress. It could represent a target for therapeutic intervention given the importance of an anaerobic environment for this organism's survival. Using protein crystallography, we have determined the three-dimensional structure of two forms of this enzyme, the wild-type rubrerythrin which is reddish in colour and a mutant protein, T48A, which is purple. The genes were cloned and expressed in E. coli and purified using liquid chromatography. Crystallization was carried out using vapor diffusion methods. Following optimization, data sets were collected to 2.2Å at the Australian Synchrotron in Melbourne. The phase problem was solved using molecular replacement. Subsequent refinement in Space Group P21212 has yielded a structure with an Rwork/Rfree of 20.6 and 27.3 respectively. The resulting rubrerythrin structure is a dimer of four-helix bundles each containing two metal centers in a geometry and fold very similar to bacterial orthologs. Kinetic studies indicate that it can function as an efficient peroxidase, but only if all sites are occupied by iron. The key to the purple color of the T48A mutant rubrerythrin appears to involve the serendipitous formation of a charge-transfer complex involving the diiron site and a tyrosine, which is facilitated by this mutation. This is the first structure reported of a eukaryotic non-haem iron peroxidase. It is a potentially important virulence factor in T. vaginalis and will serve as a basis for further work to characterize its function within the organism.

Download citation
Acta Cryst. (2014). A70, C1305
Download citation

link to html
Any listing of important scientific figures in 20th century crystallography would certainly include William Nunn Lipscomb, Jr. He is notable for both the breadth and depth of his research and because of many former students and fellows who are still active in science. Beginning with graduate work in the 40s at Caltech with Linus Pauling, his scientific career spanned almost 7 decades and produced more than 660 publications. "The Colonel" as he was known by his students was a genius in choosing important and challenging areas in which to study. He is widely known for his work on borane chemistry, theoretical chemistry and protein structure and function. His work on the chemical structure and bonding of boron cage compounds led to insights into electron deficient bonding that resulted in the award of the Nobel Prize in Chemistry in 1976. He championed the use of various quantum-mechanical approaches, both empirical and ab initio, to address questions in chemistry and biochemistry. He is particularly known for work using partial retention of differential diatomic overlap (PRDDO), and early work leading to the development of extended Hückel methods. He was a pioneer in using quantum chemistry to address questions in enzymology. His group produced the structures of several proteins including carboxypeptidase A, the 3rd enzyme structure solved after lysozyme and ribonuclease A, and also the structure of the dodecameric enzyme, aspartate transcarbamylase. The structures of the T and R forms of this protein were the first detailed descriptions of the homotropic allosteric transition ever reported for an enzyme. Additionally, Professor Lipscomb mentored a huge number of important scientists whose work continues throughout the world today. Notably two former graduate students, Tom Steitz and Roald Hoffman have received Nobel Prizes. The list of other notable group members is too long to include here but includes Don Wiley, David Christianson, Eric Gouaux, Doug Rees, Michael Rossman, and Norbert Sträter among many, many others. I was fortunate to be a graduate student with him in the 1980s and am very grateful for his influence and mentorship. With so many important scientific contributions spread over such a long time span William Lipscomb's scientific legacy is certain to endure.
Follow Acta Cryst. A
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds