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

27.03.2003


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:
http://www.stjude.org

More articles from Life Sciences:

nachricht Tag it EASI – a new method for accurate protein analysis
19.06.2018 | Max-Planck-Institut für Biochemie

nachricht How to track and trace a protein: Nanosensors monitor intracellular deliveries
19.06.2018 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

Im Focus: Photoexcited graphene puzzle solved

A boost for graphene-based light detectors

Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Carbon nanotube optics provide optical-based quantum cryptography and quantum computing

19.06.2018 | Physics and Astronomy

How to track and trace a protein: Nanosensors monitor intracellular deliveries

19.06.2018 | Life Sciences

New material for splitting water

19.06.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>