This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: In biology, a group of enzymes called 2-oxoglutarate-dependent oxygenases is responsible for catalyzing a wide range of reactions that play a role in everything from how genetic code is used by cells to the synthesis of antibiotics. Over the past several years, researchers have used ultrashort, powerful light pulses from X-ray free-electron lasers, including the Linac Coherent Light Source (LCLS) at the Department of Energy's SLAC National Accelerator Laboratory, to better understand how these enzymes catalyze reactions.
In two papers, researchers used LCLS to study the AspH enzyme—a potential therapeutic target for cancer treatment—and the isopenicillin N synthase (IPNS) enzyme, which is essential for creating penicillin. By examining those reactions step by step on timescales of mere quadrillionths of a second, they found that these enzymes activate reactions in surprising ways—leading to new insights that could inspire novel therapeutics and drug development. "We have gone from examining static structures to making 'molecular movies' of the dynamics of biological systems," said Roberto Alonso-Mori, senior scientist at SLAC.
"It has really given us an understanding of the function of proteins." The research was led by Patrick Rabe and Christopher Schofield, research group leaders at the University of Oxford in the United Kingdom, in close collaboration with Jan Kern, senior scientist at DOE's Lawrence Berkeley National Laboratory (Berkeley Lab). The research was published in Nature Communications and Nature Catalysis. In humans, the AspH enzyme is encoded by the AspH gene.
Scientists have found that levels of AspH are increased in multiple cancers, especially the hard-to-treat brain cancer called glioblastoma. By examining the structure and function of AspH and how it is regulated, scientists could potentially use the enzyme as both a biomarker and a therapeutic target for cancer treatment. Penicillin has a remarkable structure made up of two reactive rings, but as a consequence, it cannot be made by chemical synthesis.
Instead, it is made by fermentation in microbial cells. During the process of manufacturing penicillin in cells, the IPNS enzyme catalyzes a vital early-stage reaction. Analyzing how this reaction works could help scientists find a way to create synthetic modified penicillin that could overcome antibiotic resistance to better treat bacterial infections.
Researchers have studied how these enzymes catalyze reactions for years, but capturing intermediates—the molecules produced and then consumed in the middle of a reaction—has been challenging. At LCLS, researchers use macromolecular crystallography with femtosecond pulses to observe exactly what happens during these reactions. Leveraging extremely bright and short X-ray bursts, they can do so in atomic detail, on timescales of millionths of a billionth of a second, and at room temperature without damaging the biological samples.
Extract — continue reading at the source.
