Featured Research

from universities, journals, and other organizations

Enzyme's Structure Yields Blueprint For Antibiotic Resistance

Date:
August 24, 1998
Source:
Howard Hughes Medical Institute
Summary:
Starting with the structure of a common bacterial enzyme, a team of investigators from the Howard Hughes Medical Institute at The Rockefeller University has unlocked the structural secrets at the heart of some of life's most important biological processes.

August 21, 1998—-Starting with the structure of a common bacterial enzyme, a team of investigators from the Howard Hughes Medical Institute at The Rockefeller University has unlocked the structural secrets at the heart of some of life's most important biological processes.

Using x-ray crystallography, HHMI investigator Stephen K. Burley and his colleagues, working with Alex Vassilev, Yasutaka Makino and Yoshihiro Nakatani of the National Institute of Child Health and Human Development, have generated the three-dimensional molecular structure of a common enzyme, known as aminoglycoside 3-N-acetyltransferase, from the bacterium Serratia marcescens. The research is reported in the August 21, 1998, issue of the journal Cell.

According to Burley, this work has far-reaching repercussions because the bacterial enzyme's structure is shared by a superfamily of at least 150 enzymes present in every kingdom of life. Across the members of this family, says Burley, minor differences on the surfaces of the molecules generate small changes in structure, allowing them to perform a variety of biological functions.

The HHMI team determined that the bacterial enzyme's structure resembles "a cupped right hand wrapped around a cylinder." Named in part for its function, the enzyme promotes the transfer of an acetyl group from a donor molecule to a recipient molecule. "The three-dimensional structure shows us how the enzyme positions both the donor and the recipient so that the transfer can occur," Burley says.

Using a technique called "threading," Burley's team, which included Rockefeller scientists Eva Wolf and Andrej Sali, used the structure of the single enzyme they discerned to examine other members of the family of enzymes without actually having to complete x-ray crystallography on each complex. "Essentially, we thread the amino acid sequence of the unknown structures through the structure of the protein we do know and ask, 'Is it a good fit?'" Burley says. Using this technique, the researchers determined that all 150 highly conserved enzymes share the same basic structure.

Three closely related member of the acetyltransferase superfamily exist in a growing number of bacteria and they can affect humans in a potentially life-threatening manner. These enzymes transfer an acetyl group to compounds known as aminoglycosides-widely prescribed antibiotics that include gentamicin, tobramycin and netilmicin.

"The transfer inactivates these antibiotics, making them ineffective. This is an example of emerging antibiotic resistance at work," says Burley. "Now that we know the structure of the enzymes, it may become possible to design a drug that can be given along with the antibiotic. A drug that blocks the enzymes could prevent the antibiotic from being inactivated." There is precedence for such a drug, Burley says, pointing to augmentin, which blocks the part of the enzyme that inactivates the antibiotic penicillin.

Other important acetyltransferases abound. One enzyme with the same fundamental structure is responsible for the final chemical step in synthesizing a neurotransmitter important in the control of mood, depression and anxiety. In another incarnation, a structurally similar enzyme acts as a switch that frees DNA to become active and begin expressing messenger RNA. Such widespread biological activity gives the discovery importance for a wide range of investigations.

Discerning the common structure of such a large family of enzymes also provides an important clue to understand how proteins accomplish life's functions. Burley explains that although there are some 100,000 human genes, they produce only about 2,000 basic protein structures. Slightly different surfaces give the proteins their unique chemical properties and abilities, but in many cases, their basic structures are shared. "We now know one more of the fundamental structures," Burley says.


Story Source:

The above story is based on materials provided by Howard Hughes Medical Institute. Note: Materials may be edited for content and length.


Cite This Page:

Howard Hughes Medical Institute. "Enzyme's Structure Yields Blueprint For Antibiotic Resistance." ScienceDaily. ScienceDaily, 24 August 1998. <www.sciencedaily.com/releases/1998/08/980824072624.htm>.
Howard Hughes Medical Institute. (1998, August 24). Enzyme's Structure Yields Blueprint For Antibiotic Resistance. ScienceDaily. Retrieved October 2, 2014 from www.sciencedaily.com/releases/1998/08/980824072624.htm
Howard Hughes Medical Institute. "Enzyme's Structure Yields Blueprint For Antibiotic Resistance." ScienceDaily. www.sciencedaily.com/releases/1998/08/980824072624.htm (accessed October 2, 2014).

Share This



More Health & Medicine News

Thursday, October 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pregnancy Spacing Could Have Big Impact On Autism Risks

Pregnancy Spacing Could Have Big Impact On Autism Risks

Newsy (Oct. 1, 2014) A new study says children born less than one year and more than five years after a sibling can have an increased risk for autism. Video provided by Newsy
Powered by NewsLook.com
Robotic Hair Restoration

Robotic Hair Restoration

Ivanhoe (Oct. 1, 2014) A new robotic procedure is changing the way we transplant hair. The ARTAS robot leaves no linear scarring and provides more natural results. Video provided by Ivanhoe
Powered by NewsLook.com
Insertable Cardiac Monitor

Insertable Cardiac Monitor

Ivanhoe (Oct. 1, 2014) A heart monitor the size of a paperclip that can save your life. The “Reveal Linq” allows a doctor to monitor patients with A-Fib on a continuous basis for up to 3 years! Video provided by Ivanhoe
Powered by NewsLook.com
Attacking Superbugs

Attacking Superbugs

Ivanhoe (Oct. 1, 2014) Two weapons hospitals can use to attack superbugs. Scientists in Ireland created a new gel resistant to superbugs, and a robot that can disinfect a room in minutes. Video provided by Ivanhoe
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