SSRL Science Highlight: Research Sheds Light on Workings of Anti-cancer Drug

Structure of the nest-shaped copper-binding cluster in the TM-copper-protein complex with average interatomic distances. (Image courtesy the researchers.)

from SSRL Headlines

Cells need copper to function, but too much copper can be toxic, leading to liver damage and neurological problems, as happens in disorders such as Wilson disease. The inorganic small molecule tetrathiomolybdate, or TM, assumed to be a copper chelator, is commonly used to treat Wilson disease. TM may also be an effective treatment of some cancers, acting by starving the cancer cells of the copper they need to grow. Despite its common use, TM's molecular mechanism was unknown.

A team of researchers led by Thomas O'Halloran and Alfonso Mondragon of Northwestern University and Jim Penner-Hahn of University of Michigan used Beamline 9-3 at the Stanford Synchrotron Radiation Lightsource to determine the structure of TM bound to copper and its chaperone protein. They were surprised to find that TM does not simply sequester copper from the copper chaperone, but binds to a nest-shaped copper-protein complex, completely disrupting the copper transport system.

Understanding how TM can shut down the copper ferrying system could lead to treatments for some cancers, since growing cancers require a supply of copper. TM may also be useful for treating other diseases, such as familial amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, Alzheimer's disease and some disorders associated type II diabetes. The research was published in the January 15 issue of Science.

To learn more about this research see the full scientific highlight.

Colloquium Next Monday:
The Mars Science Laboratory

There will be no colloquium today.

Next Monday at 4:15 p.m. in Panofsky Auditorium, Adrian Brown of the SETI Institute and NASA Ames Research Center will present "Mars Science Laboratory Mission and the Search for Carbonates and Methane on Mars."

The Mars Science Laboratory (named "Curiosity") will launch to Mars next year and is loaded with new instruments and cameras to investigate the geology of a new location on Mars. Brown will talk about the exciting and scary aspects of the new rover, and how it might just impact our understanding of the chances for life on the Red Planet. The MSL Rover will have the capability to measure atmospheric methane, which is a possible trace gas for Martian volcanism or perhaps even Martian biota. Brown will discuss the recent controversy over methane, and how it is linked to the 2008 finding of carbonate on Mars.

The colloquium is free and open to the public.

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Six New Planets Discovered Physorg
AFM Tip 'Writes' Graphene Nanowires Physicsworld
The Smithsonian and Synchrotron Soleil Join to Analyze Antiquities, Cultural Heritage Materials Smithsonian

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SSRL Science Highlight: Research Sheds Light on Workings of Anti-cancer Drug Structure of the nest-shaped copper-binding cluster in the TM-copper-protein complex with average interatomic distances. (Image courtesy the researchers.) from SSRL Headlines Cells need copper to function, but too much copper can be toxic, leading to liver damage and neurological problems, as happens in disorders such as Wilson disease. The inorganic small molecule tetrathiomolybdate, or TM, assumed to be a copper chelator, is commonly used to treat Wilson disease. TM may also be an effective treatment of some cancers, acting by starving the cancer cells of the copper they need to grow. Despite its common use, TM's molecular mechanism was unknown. A team of researchers led by Thomas O'Halloran and Alfonso Mondragon of Northwestern University and Jim Penner-Hahn of University of Michigan used Beamline 9-3 at the Stanford Synchrotron Radiation Lightsource to determine the structure of TM bound to copper and its chaperone protein. They were surprised to find that TM does not simply sequester copper from the copper chaperone, but binds to a nest-shaped copper-protein complex, completely disrupting the copper transport system. Understanding how TM can shut down the copper ferrying system could lead to treatments for some cancers, since growing cancers require a supply of copper. TM may also be useful for treating other diseases, such as familial amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, Alzheimer's disease and some disorders associated type II diabetes. The research was published in the January 15 issue of Science. To learn more about this research see the full scientific highlight. Colloquium Next Monday: The Mars Science Laboratory There will be no colloquium today. Next Monday at 4:15 p.m. in Panofsky Auditorium, Adrian Brown of the SETI Institute and NASA Ames Research Center will present "Mars Science Laboratory Mission and the Search for Carbonates and Methane on Mars." The Mars Science Laboratory (named "Curiosity") will launch to Mars next year and is loaded with new instruments and cameras to investigate the geology of a new location on Mars. Brown will talk about the exciting and scary aspects of the new rover, and how it might just impact our understanding of the chances for life on the Red Planet. The MSL Rover will have the capability to measure atmospheric methane, which is a possible trace gas for Martian volcanism or perhaps even Martian biota. Brown will discuss the recent controversy over methane, and how it is linked to the 2008 finding of carbonate on Mars. The colloquium is free and open to the public.	Events (see all \| submit) Jun 15 (12:30 p.m.) Experimental Seminar: Status and Prospects for the SuperCDMS and GEODM Access (see all) Turnstile at Sector 27 Closed Work in SSRL Parking Lot/Road to Research Yard No Storage in Former RV Area Announcements (see all \| submit) Lab Announcements Deadline for Performance Evaluation Meetings Jul 7 Community Bulletin Board Juneteenth Celebration T-Shirts and Caps for Sale Juneteenth Celebration Jun 18 Training ((see all \| register) Lab Training Calendar Registration Today (1:30 p.m.) Fire Extinguisher Training Upcoming Workshops & Classes Online Tech Training Opportunities News (submit) Six New Planets Discovered Physorg AFM Tip 'Writes' Graphene Nanowires Physicsworld The Smithsonian and Synchrotron Soleil Join to Analyze Antiquities, Cultural Heritage Materials Smithsonian
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