Uploaded September 2024 | Updated September 2026, 1 week ago
Serine hydroxymethyltransferase, or SHMT is a tetramer constructed from four identical peptide chains, or protomers, shown in gray. SHMT is an unusual enzyme that functions by using two vitamins — B6 and B9. Vitamin B6, or pyridoxal-5′-phosphate, shown in gold, is covalently attached to a specific lysine amino acid inside the enzyme’s active site. But tetrahydrofolate, shown in purple, is a derivative of folic acid (vitamin B9) that acts as a substrate that binds noncovalently to the active site in all four protomers. The exact catalytic mechanism and the roles of various amino acid residues in the enzyme’s active sites have been debated for decades.
Neutrons revealed the locations and movement of hydrogen atoms, shown flashing in green, that play indispensable roles in promoting the catalytic reaction, allowing researchers at ORNL to examine the active site in never-before-seen atomic detail. The locations of the hydrogen atoms determine protonation states of specific chemical groups inside the active site. Thus, they provide information on the electric charge distribution. This knowledge is crucial for designing small-molecule inhibitors that would bind to SHMT and arrest the enzyme’s function. Such inhibitors, shown in blue, could be developed into a new class of anticancer drugs. Read more here: ornl.gov/news/neutrons-seek-stop-cancer-hijacking-metabolic-highway and here: ornl.gov/news/case-closed-neutrons-settle-40-year-debate-enzyme-drug-design
Credit: Phoenix Pleasant/ORNL, U.S. Dept. of Energy
@Energy @doescience #science #energy #research
Serine hydroxymethyltransferase, or SHMT is a tetramer constructed from four identical peptide chains, or protomers, shown in gray. SHMT is an unusual enzyme that functions by using two vitamins — B6 and B9. Vitamin B6, or pyridoxal-5′-phosphate, shown in gold, is covalently attached to a specific lysine amino acid inside the enzyme’s active site. But tetrahydrofolate, shown in purple, is a derivative of folic acid (vitamin B9) that acts as a substrate that binds noncovalently to the active site in all four protomers. The exact catalytic mechanism and the roles of various amino acid residues in the enzyme’s active sites have been debated for decades.
Neutrons revealed the locations and movement of hydrogen atoms, shown flashing in green, that play indispensable roles in promoting the catalytic reaction, allowing researchers at ORNL to examine the active site in never-before-seen atomic detail. The locations of the hydrogen atoms determine protonation states of specific chemical groups inside the active site. Thus, they provide information on the electric charge distribution. This knowledge is crucial for designing small-molecule inhibitors that would bind to SHMT and arrest the enzyme’s function. Such inhibitors, shown in blue, could be developed into a new class of anticancer drugs. Read more here: ornl.gov/news/neutrons-seek-stop-cancer-hijacking-metabolic-highway and here: ornl.gov/news/case-closed-neutrons-settle-40-year-debate-enzyme-drug-design
Credit: Phoenix Pleasant/ORNL, U.S. Dept. of Energy
@Energy @doescience #science #energy #research
![What Does ORNL Do? [Full version]](https://i.ytimg.com/vi/8a_CYizL-ss/mqdefault.jpg "What Does ORNL Do? [Full version]
In the eight decades since Oak Ridge National Laboratory’s founding, our research has advanced understanding of the world around us — while building foundational infrastructure and expertise to support scientific discovery globally. From energy and the environment to human health and national security, ORNL is committed to solving the challenges that matter to you. Learn more: https://www.ornl.gov/bigscience
#science #energy #research")
