Featured Research

from universities, journals, and other organizations

Researchers Design New Way To Squelch Errant Enzymes

Date:
January 22, 2001
Source:
Johns Hopkins Medical Institutions
Summary:
Scientists at Johns Hopkins, New York University and Mount Sinai School of Medicine in New York have found a way to block the action of specific enzymes with a pivotal role in triggering cancers, hardening of the arteries and certain autoimmune diseases.

Scientists at Johns Hopkins, New York University and Mount Sinai School of Medicine in New York have found a way to block the action of specific enzymes with a pivotal role in triggering cancers, hardening of the arteries and certain autoimmune diseases.

Related Articles


Their research, described in this month's Nature Structural Biology, explains how a blockading molecule, called a bisubstrate analog, effectively prevents protein kinase enzymes from docking with other molecules in the body — in short, from working. "The bisubstrate analogs are extremely potent in inhibiting reactions," says Philip A. Cole, M.D., Ph.D., who led the research.

The researchers designed the bisubstrate analog using an improved understanding of how protein kinases normally work at the molecular level. They liken their work to the science that produced the protease inhibiting drugs that tipped the disease scales from fatal to chronic for many AIDS sufferers. "We don't have a drug for patients yet, but this is still a real advance in the field," Cole adds.

Protein kinases are widespread in the body. "About 2 percent of our genes code for protein kinases," says Cole. The enzymes help ferry a small, reactive cluster of atoms containing phosphorus — called a phosphoryl group — to cell proteins. Once thought to be a mere housekeeping procedure, this transfer, researchers now know, is crucial to cells. Once a protein gains a phosphoryl group, Cole says, the protein changes, becoming a key player in cell reactions that prompt growth and reproduction.

"Our work may be particularly helpful in developing therapies for cancers," says Cole, "which can stem from mutations in genes that regulate kinases." Experiments show that too much of a particular kinase can lead to tumors, and that autoimmune diseases such as arthritis and other inflammatory conditions probably involve kinases that are too efficient or overactive. "Finding a way to inhibit them is probably a very good idea," Cole adds.

Unlike other approaches to block protein kinases, the researchers say, the new technique works both on the molecules that donate the phosphoryl groups and on the protein molecules that accept them. Their bisubstrate analog simultaneously attaches to both molecules, crowding out protein kinases.

Most important, Cole says, is that their approach targets specific protein kinases. "There are probably several thousand different kinases with roles in different disease pathways. The biggest problem has been singling out specific ones to inhibit," he says. Minor tinkering with bisubstrate analogs may produce a wide variety of the molecular red herrings, each designed to counteract a specific protein kinase.

Cole's team now plans versions of the analogs that can persist long enough in the human body to be useful therapy. Grants from the National Institutes of Health and the Burroughs Wellcome Fund supported the research. The researchers have applied for a patent on the bisubstrate analog.

Other researchers are Keykavous Parang, Ph.D., recently at Johns Hopkins but now at the University of Rhode Island, Jeffrey H. Till and Stevan R. Hubbard with the New York University School of Medicine, and Ararat J. Ablooglu and Ronald A. Kohanski at the Mount Sinai School of Medicine in New York city.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medical Institutions. "Researchers Design New Way To Squelch Errant Enzymes." ScienceDaily. ScienceDaily, 22 January 2001. <www.sciencedaily.com/releases/2001/01/010118065110.htm>.
Johns Hopkins Medical Institutions. (2001, January 22). Researchers Design New Way To Squelch Errant Enzymes. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2001/01/010118065110.htm
Johns Hopkins Medical Institutions. "Researchers Design New Way To Squelch Errant Enzymes." ScienceDaily. www.sciencedaily.com/releases/2001/01/010118065110.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Christmas Kissing Good for Health

Christmas Kissing Good for Health

Reuters - Innovations Video Online (Dec. 22, 2014) Scientists in Amsterdam say couples transfer tens of millions of microbes when they kiss, encouraging healthy exposure to bacteria. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Brain-Dwelling Tapeworm Reveals Genetic Secrets

Brain-Dwelling Tapeworm Reveals Genetic Secrets

Reuters - Innovations Video Online (Dec. 22, 2014) Cambridge scientists have unravelled the genetic code of a rare tapeworm that lived inside a patient's brain for at least four year. Researchers hope it will present new opportunities to diagnose and treat this invasive parasite. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins