Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


St. Jude researchers decipher structure, activity of enzyme key to biochemical pathways of life


Finding how E1 enzyme juggles three jobs should lead to critical insights into the control of cellular functions at the heart of health and disease

Scientists at St. Jude Children’s Research Hospital have discovered how a single enzyme called E1 performs a rapid-fire, three-part chemical makeover of a protein that helps control some of the most fundamental biochemical processes of the human cell. The enzyme uses two different parts of its own structure to juggle four different molecules as it completes three different reactions.

This rare ability of a single enzyme to carry out three different chemical reactions by itself is at the heart of the role E1 plays in modifying NEDD8, which is part of a family of proteins called ubiquitin-like proteins. E1 proteins are a family of molecules called activating enzymes.

These enzymes coordinate the activity of different ubiquitin-like proteins.

The cell uses ubiquitin-like proteins such as NEDD8 to trigger special molecules that act as on switches for a variety of biochemical pathways, according to Brenda Schulman, Ph.D., an assistant member of the St. Jude Departments of Structural Biology, Genetics and Tumor Cell Biology.

The pathways switched on by ubiquitin-like proteins include vital activities, such as immune responses and cell division, she said. Schulman is the senior author of a report appearing in the March 20 issue of Nature on the structure and function of the E1 activating enzyme for NEDD8.

"The cell uses E1 activating enzymes to keep a tight rein on all of the various biochemical pathways it must activate," Schulman said. "Otherwise the cell would be chaotic and wouldn’t be able to perform the tasks it is supposed to do in the body."

Each type of E1 activating enzyme coordinates a specific function to make sure it occurs at precisely the right time, she says.

The complex series of reactions that control each function begins when a specific E1 activating enzyme combines an ubiquitin-like protein such as NEDD8 to an "escort" molecule.

The escort brings the ubiquitin-like protein to its pre-assigned target molecule. When the ubiquitin-like protein chemically modifies this molecule, the molecule triggers a specific cellular activity, such as cell division.

The discovery of the structure of the E1 activating enzyme for NEDD8 helps explain the critical steps by which E1 links NEDD8 to its E2 escort.

"Now that we know exactly what the E1 for NEDD8 looks like and how it works, we can start to understand how the cell controls its extraordinarily complex command and control systems," Schulman said. "We’ll start to understand how the cell gets through the day doing its jobs and keeping us healthy--or making us ill when its command and control systems get disrupted."

For example, the influenza virus hijacks one of the ubiquitin-like proteins so it does not undergo its normal activation by an E1 enzyme.

This hijacking helps the virus hide from the surveillance system set up by the immune system to track infections.

"The more we learn about how these pathways are controlled, the more likely we’ll understand how to fix them when they get disrupted and cause a wide variety of diseases," Schulman said.

Schulman and her colleagues obtained the information that let them create a picture of the E1 structure using a technique called X-ray crystallography. In this technique, the proteins are first crystallized to immobilize them, and then X-rays are directed at the protein crystal.

The pattern formed by the x-rays as they bounce off the protein crystal is then translated into a picture of the molecule.

Other authors of the paper include Helen Walden, Ph.D. and Michael S. Podgorski, both of St. Jude.

The work was supported by ALSAC, the National Cancer Institute Cancer Center (CORE) and a Pew Scholar in Biomedical Science Award to ’Schulman.

St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital’s work is supported through funds raised by ALSAC. ALSAC covers all costs not covered by insurance for medical treatment rendered at St. Jude Children’s Research Hospital. Families without insurance are never asked to pay. For more information, please visit http://.

Bonnie Cameron | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>