Corporate Banner
Satellite Banner
Crystallography
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Wistar Scientists Decipher Structure of NatA, an Enzyme Complex that Modifies Most Human Proteins

Published: Wednesday, August 07, 2013
Last Updated: Wednesday, August 07, 2013
Bookmark and Share
A team of researchers has determined the structure of an enzyme complex that modifies one end of most human proteins and is made at elevated levels in numerous forms of cancer.

A study in Nature Structural & Molecular Biology, led by researchers at The Wistar Institute, depicts the structure and the means of action of a protein complex called NatA.  Their findings, they believe, will allow them to create an inhibitor—a potential drug—that could knock out NatA in order to curb the growth of cancer cells.

“NatA appears essential for the growth of cells and their ability to divide, and we can see elevated production of this enzyme in many forms of cancer” said Ronen Marmorstein, Ph.D., senior author, Hilary Koprowski, M.D. Professor, and leader of The Wistar Institute Cancer Center’s Gene Expression and Regulation program. “Obviously, this is a particularly appealing drug target and we are currently leveraging our recent understanding of how the protein works to develop small molecules that will bind to and inactivate NatA.”

NatA is a member of a family of N-terminal acetyltransferase (NAT) enzymes (or enzyme complexes) that modify proteins in order to control their behavior—for example by turning proteins on, telling proteins where to move, and tagging proteins or the cell for destruction.

According to Marmorstein, NatA works with an amazing specificity for a particular sequence of amino acids—the individual building blocks of proteins—and unraveling the roots of that specificity has proven an alluring puzzle for scientists.

The Marmorstein laboratory has proven expertise in the study of acetylation enzymes, proteins that modify other molecules in the cell with an acetyl group “tag.” In the cellular world, structure dictates function, and acetylation is a universal process for controlling protein behavior and gene expression in living organisms.

“Modifying protein structures is one way that our cells control how proteins function,” Marmorstein explained, “and enzymes in the NAT family modify nearly 85 percent of human proteins, and 50 percent of these are modified by NatA.”

According to Marmorstein, NatA operates in a complex of two proteins, an enzymatic subunit and an auxiliary partner. When they developed the structure of NatA—by bombarding a crystallized sample of the enzyme with powerful X-rays—they found how the auxiliary partner protein is crucial for turning the enzymatic subunit on.

Binding to an auxiliary protein causes a structural change in the enzymatic subunit that properly configures the active site of the protein—the region of the protein where the chemical reaction occurs—essentially acting as a switch that activates the enzyme.

“When it binds to its auxiliary protein, the enzymatic subunit of NatA actually changes shape, reconfiguring the structure to allow it to properly grab its target protein N-terminal sequence for acetylation,” Marmorstein said.

Importantly, others have found that NatA function is required for the proliferation of cancer cells. Marmorstein says, understanding the structure of NatA has allowed his team to better understand how to inactivate the protein in cancer cells. The structure has yielded targets for small molecules that will act as inhibitors, essentially stopping the protein by gumming up its structure.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More than 4,600+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Scientists Solve Structure of Gene Regulator that Plays Key Role in Cancer
Scientists at The Wistar Institute have collaborated on a major advance in understanding a gene regulator that contributes to some of the deadliest cancers in humans.
Friday, February 15, 2008
Telomerase Enzyme Structure Provides Significant New Target for Anti-Cancer Therapies
Findings made by researchers at The Wistar Institute may also provide insights into normal aging.
Thursday, November 15, 2007
Scientific News
Molecular Map Provides Clues To Zinc-Related Diseases
Mapping the molecular structure where medicine goes to work is a crucial step toward drug discovery against deadly diseases.
What Makes a Good Scientist?
It’s the journey, not just the destination that counts as a scientist when conducting research.
CaSR Role in Maintaining Calcium Concentration Uncovered
Georgia State-led study paves way for new therapies in fight against calcium disorders.
3-D Atomic Structure of Cholesterol Transporter
Researchers at UTSW have determined the 3-D atomic structure of a human sterol transporter that helps maintain cholesterol balance.
Neutron Analysis of HIV-1 Protease
Neutrons probe structure of enzyme critical to development of next-generation HIV drugs.
Do Germs Cause Type 1 Diabetes?
Germs could play a role in the development of type 1 diabetes by triggering the body’s immune system to destroy the cells that produce insulin, new research suggests.
Crucial Reaction for Vision Revealed
Scientists have tracked the reaction of a protein responding to light, paving the way for a new understanding of life's essential reactions.
Secrets of a Deadly Virus Family Revealed
Scripps Research scientists uncover the glycoprotein structure of LCMV. The findings could guide development of treatments for Lassa fever.
Serotonin Transporter Structure Revealed
Researchers determined the 3-D structure of the serotonin transporter and visualized how two common antidepressants interact with the protein.
Zika Virus Structure Revealed
Team at Purdue becomes the first to determine the structure of the Zika virus, which reveals insights critical to the development of effective antiviral treatments and vaccines.
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,600+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!