[Bill Duax] William L. Duax

When I began editing the IUCr Newsletter in 1992, I was impressed with the fact that exciting and important new crystal structure reports appeared weekly in Science, Nature and other leading journals in chemical, biological and materials science. Because the structures were not only important but also esthetically pleasing they often wound up on the covers of the journals. I began collecting many of the articles and planned to highlight them in the IUCr Newsletter. Although I collected (and discarded) many thousands of these articles over the past 20 years, I never found the time to write summaries of what I thought of as Hot New Structures.

On the eve of the International Year of Crystallography, I decided it was time to try to write such a column for the IUCr Newsletter. I invite readers to send brief comments on recent crystal structure reports that they consider of exceptional importance to be included in such a column. Because crystallography contributes to significant advances in so many fields, I am hardly qualified to identify what is 'Hot' in every area.

I would be pleased to have volunteers willing to cover specific parts of the wide range of crystallographic theory, methods, techniques, instrumentation and applications in regular columns in the IUCr Newsletter.

Here are notes on some of the newsworthy X-ray crystal structures that have been published in leading journals in the past three months. My bias toward biological structures is obvious.

[Ergotamine] Crystal structure of the chimeric protein of 5-HT2B-BRIL in complex with ergotamine. (PDB DOI: 10.2210/pdb4ib4/pdb)

Seratonin is a ligand for a family of 15 receptors and is used to treat migraine headache, depression, anxiety, nausea, vomiting and irritable bowel syndrome. Crystal structures of complexes of two different serotonin receptors with the antimigraine agent ergotamine [Wacker et al., Science (2013), 340, 615; Wang et al., Science (2013), 340, 610], revealed differences in the ways ligands bind to the receptors that lead to different biological responses.

Rapamycin is an immunosuppressant extensively used to prevent rejection of transplanted kidneys, livers and hearts. The growth-signaling enzyme mTOR that plays a critical role in cancer and immunity is inhibited by rapamycin binding. The crystal structure of the complex of mTOR and rapamycin [Pavletich et al., Nature (2013), 38, 10] reveals how mTOR and its inhibitors work.

Point mutations of three active site residues in isocitrate dehydrogenase (IDH) define distinct cancers (a sarcoma, a carcinoma and a leukemia). Wang et al. [Science (2013), 340, 622] synthesized an inhibitor of IDH and determined the complex of IDH and the inhibitor. The structure suggests how specific mutants of IDH might be targeted for specific cancers.

[Sepiapterin] Crystal structure of human sepiapterin reductase in complex with sulfapyridine. (PDB DOI: 10.1126/science.1232972)

The use of sulfa drugs to combat bacterial infection began in 1935. The mechanism of action is known but the molecular basis for side effects remains an open question. The crystal structure of sepiapterin reductase with bound sulfa drugs reveals how some different sulfa drugs achieve selective enzyme inhibition [Haruki et al., Science (2013), 340, 987].

[Parkin domain] Crystal structure of Parkin C-terminal RING domains. PDB DOI: 10.2210/pdb4k7d/pdb)
[Parkin] Crystal structure of Parkin. (PDB DOI: 10.2210/pdb4k95/pdb)

Mutations in PARK@(parkin) gene are responsible for a form of Parkinson's disease. The crystal structure of rat parkin [Trempe et al., Science (2013), 340, 1451] provides insight into how it is activated and may lead to ways to enhance its activity.

Metal-organic frameworks offer pore geometries that facilitate distinct types of shape-based molecular separations. An iron benzenedipyrazolate forms a stable framework with triangular channels that can separate hexane isomers according to degree of branching, as determined by powder Xray diffraction techniques [Herm et al., Science (2013), 340, 960].

William L. Duax