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May 22, 2018

A New Guide for Explorers of the Submicroscopic World Inside Us

An illustration of architecture from the submicroscopic world, created with knowledge gleaned through X-ray crystallography.

Researchers from the School of Medicine have established new guidelines for scientists mapping out the body molecule by molecule to help us better understand how our cells use metals such as iron and magnesium to maintain good health. The guidelines ultimately will benefit the battle against diseases such as cancer, assist in the development of new drugs and ensure scientific results are accurate and can be reproduced.

The new protocols aim to help scientists in the field of X-ray crystallography avoid potential pitfalls that could inadvertently compromise their work. X-ray crystallography reveals things far smaller than a scientist using a traditional light microscope could ever hope to see. It works a bit like sonar – scientists bombard molecules with X-rays, then measure the angles as the X-rays bounce off, or “diffract.” They can then use that information to calculate the shape of their target.

It’s a tremendously complex undertaking, of course, and there are many ways for it to go wrong. The new technical guidelines, from a team led by Wladek Minor, PhD, aim to prevent that.

“The compilation of the best practices and potential pitfalls for the accurate characterization of a metal binding site in any protein or virus is no easy task, and requires years of combined experience and efforts from many researchers from different areas of expertise,” said Minor, of the Department of Molecular Physiology and Biological Physics. “We hope that our research will improve the quality and reliability of research that involves handling metal-containing samples and eventually contribute to promoting research reproducibility in both academic and commercial settings.”

Forging the Way

Wladek Minor and his colleagues have developed new guidelines for scientists exploring how the human body uses metals to maintain good health.
Wladek Minor and his colleagues have developed new guidelines for scientists exploring how the human body uses metals to maintain good health.

Minor – who is already an author of one of the most cited scientific papers of all time – noted that metals play essential roles in many biological and cellular processes. “In the human circulatory system, for example,” he said, “serum albumin transports zinc, while iron in hemoglobin is crucial for oxygen transport to all cells, and magnesium is a component of many enzymes.”

In addition, there is an entire class of cancer drugs that is metal-based. So it is critical we have an accurate understanding of how the body interacts with metals.

“Misidentification and/or misinterpretation of metal binding sites in proteins and nucleic acids may hamper data interpretation and negatively influence future studies,” said Heping Zheng, the co-corresponding author of the paper. “Biologists, pharmacologists and scientists involved in metal-based drug development should benefit from our studies.”

Crystallography Guidelines Published

The new crystallography guidelines have been published in the scientific journal Nature Protocols. The article was featured as the journal’s cover story. It was written by Katarzyna B. Handing, Ewa Niedzialkowska, Ivan G. Shabalin, Misty L Kuhn, Zheng and Minor. Reporters covering the new guidelines are asked to link to the article in their online stories:

The work was supported by the National Institutes of Health’s National Institute of General Medical Sciences, grants GM117325 and GM117080; NIH BD2K grant HG008424; the National Institute of Allergy and Infectious Diseases under contracts HHSN272201200026C and HHSN272201700060C.

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