Corporate Banner
Satellite Banner
RNAi
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 3,500+ scientific posters on ePosters
  • More than 5,000+ 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

New Insight into Pre-Birth Cancer Development
Cells responsible for the development of leukaemia in the womb have been identified, adding to knowledge of this aggressive cancer type.
Friday, July 08, 2016
Graham Cancer Center, The Wistar Institute Partner
Partnership aims to accelerate breakthrough cancer research in the human genome.
Thursday, June 30, 2016
Aging Impacts Therapeutic Response of Melanoma Cells
Researchers at Wistar Institute have showed that tumor cells in aged skin behave differently than tumor cells in younger skin.
Friday, April 08, 2016
Genetic Variant and Bacteria Help Dictate Inflammation, Antitumor Activity, and Outcome in Cancer Patients
Research reveals more about the role the symbiotic relationship humans have with bacteria may play in tumor progression.
Monday, December 22, 2014
Scientific News
Fighting Cancer with Sticky Nanoparticles
Treatment that uses bioadhesive nanoparticles drug carriers proved more effective than conventional treatments for certain cancers.
Fighting Plant Pathogens with RNA
Researchers develop strategy that could lead to environmentally friendly fungicide to fight pathogens.
Smart Material Hunts Cancers
Team has created smart material that locates and images cancer or tumour sites in tissue.
Examining mtDNA May Help Identify Unknown Ancestry That Influences Breast Cancer Risk
Researchers studying mtDNA in a group of triple negative breast cancer patients found that 13 percent of participants were unaware of ancestry that could influence their risk of cancer.
Gene Therapy Technique May Help Prevent Cancer Metastasis
Gene-regulating RNA molecules could help treat early-stage breast cancer tumors before they spread.
Enhancing Antibiotics to Defeat Resistant Bacteria
Scientists enhance ability of antibiotics to defeat resistant types of bacteria using molecules called PPMOs
MRI Guidance Aids Stem Cell Delivery
Scientists have delivered stem cells to the brain with unprecedented precision, infusing the cells under real-time MRI guidance.
High-Capacity Nanoparticles
New type of nanoparticle can now have three or more drugs packaged within it, allowing for customised cancer therapy.
UTSW Creates Nanoparticles That Target Lung Cancer Cells
Researchers at UTSW have developed a synthetic polymers that could deliver nucleic acid drugs while possessing enough structural diversity to discover cancer cell-specific nanoparticles.
Delivering Beneficial Bacteria
Method that transports microbes through the stomach to the intestine may benefit human health.
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
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!