Navigation Links
Wistar scientists decipher structure of NatA, an enzyme complex that modifies most human proteins
Date:8/4/2013

A team of researchers from Philadelphia and Norway 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 inhibitora potential drugthat 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 behaviorfor 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 acidsthe individual building blocks of proteinsand 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 NatAby bombarding a crystallized sample of the enzyme with powerful X-raysthey 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 proteinthe region of the protein where the chemical reaction occursessentially 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.


'/>"/>

Contact: Greg Lester
glester@wistar.org
215-898-3934
The Wistar Institute
Source:Eurekalert

Related biology news :

1. It takes two to tangle: Wistar scientists further unravel telomere biology
2. High folate gestational and post-weaning diets in Wistar rat offspring
3. Stanford scientists develop gene therapy approach to grow blood vessels in ischemic limbs
4. Queens scientists seek vaccine for Pseudomonas infection
5. Scientists produce eye structures from human blood-derived stem cells
6. American Society of Plant Biologists honors early career women scientists
7. Brandeis scientists win prestigious prize for circadian rhythms research
8. Scientists discover new method of proton transfer
9. Salk scientists open new window into how cancers override cellular growth controls
10. WileyChina.com - Now Featuring Bespoke Pages for China’s Life Scientists
11. Scientists win $2 million to study new pathway in development and maintenance of lymphoma
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/7/2016)... , June 7, 2016  Syngrafii Inc. ... a business relationship that includes integrating Syngrafii,s patented ... branch project. This collaboration will result in greater ... the credit union, while maintaining existing document workflow ... http://photos.prnewswire.com/prnh/20160606/375871LOGO ...
(Date:6/1/2016)... June 1, 2016 Favorable Government ... Administration and Criminal Identification to Boost Global Biometrics System ... released TechSci Research report, " Global Biometrics Market ... Forecast and Opportunities, 2011 - 2021", the global biometrics ... 2021, on account of growing security concerns across various ...
(Date:5/9/2016)... 2016 Elevay is currently known ... freedom for high net worth professionals seeking travel for ... connected world, there is still no substitute for a ... sealing your deal with a firm handshake. This is ... advantage of citizenship via investment programs like those offered ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 23, 2016 /PRNewswire/ - FACIT has announced the ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or ... of a portfolio of first-in-class WDR5 inhibitors for ... as WDR5 represent an exciting class of therapies, ... medicine for cancer patients. Substantial advances have been ...
(Date:6/23/2016)... 2016  The Biodesign Challenge (BDC), a university competition ... harness living systems and biotechnology, announced its winning teams ... New York City . The ... projects at MoMA,s Celeste Bartos Theater during the daylong ... senior curator of architecture and design, and Suzanne ...
(Date:6/23/2016)... Ky. , June 23, 2016 ... two Phase 1 clinical trials of its complement ... placebo-controlled, single and multiple ascending dose studies designed ... pharmacodynamics (PD) of subcutaneous injection in healthy adult ... subcutaneously (SC) either as a single dose (ranging ...
(Date:6/23/2016)... ... June 23, 2016 , ... Regulatory Compliance Associates® Inc. (RCA), ... free webinar on Performing Quality Investigations: Getting to Root Cause. ... no charge. , Incomplete investigations are still a major concern to the Regulatory ...
Breaking Biology Technology: