Featured Research

from universities, journals, and other organizations

Long-awaited Atomic Structure Of Well-known Enzyme Solved: Discovery Heralds New Approaches To Protein-engineered Biofuels

Date:
May 21, 2009
Source:
Boston University Medical Center
Summary:
Researchers have identified the structural underpinnings of AADase, a widely known enzyme that was described correctly 43 years ago. However, it lacked a complete structural explanation. The original electrostatic perturbation hypothesis did not have a definitive structural elucidation -- until now. Using X-ray crystallography, researchers provide the missing structure that explains the original hypothesis about microenvironmental control of enzyme reactions within the cell.

A Boston University–led research team has identified the structural underpinnings of a widely-known enzyme -- acetoacetate decarboxylase (AADase) -- that was first described correctly more than 43 years ago including how it accelerates its target reaction. Until now it has never been fully explained how the reactions occur in the environment of the cell.

Related Articles


Enzymes catalyze, or speed-up, chemical processes by accomplishing in seconds what otherwise might take hours, days or centuries to happen spontaneously. AADase is the catalyst that that converts acetoacetate to acetone, a key component in the metabolism of carbohydrates in bacteria and a historically important enzyme whose industrial development – the conversion of acetoacetate to acetone -- for cordite, the colorless, flammable substance used during World War 1 to make explosives for naval guns and as a coating for military airplane wings.

Back then Chaim Weiszmann, a Russian chemist living in England isolated a bacterium that transforms cornstarch to a mixture of acetone, a common building block in organic chemistry, and several alcohols – a major improvement over an inefficient wood distillation process in use at that time. The manufacturing process, which was developed and scaled up with U.S. and Canadian help, ultimately enabled the British in 1917 to win the war over Germany.

In the 1960s, AADase was used by Dr. Frank H. Westheimer, a Harvard University chemistry professor, to pioneer the application of methods in physical organic chemistry for the study of the chemical and catalytic mechanism of enzymes. He developed a hypothesis about how enzymes worked, and how a protein could control its own environment around the reaction. By changing the interior of a protein, chemical reactions occurred that were different from those that can occur in solution and from those that occur in other enzymes in the cell.

Missing from Westheimer's model was a structural explanation that would show the basis for his electrostatic perturbation hypothesis. Although the hypothesis has been demonstrated in a number of enzymes, there were assumptions made about the complex three-dimensional shape -- or protein fold which provides AADase's structure.

By defining AADase atomic structure using X-ray crystallography, the research team corrects those assumptions and provides the missing structure that explains Westheimer's hypothesis about microenvironmental control of enzyme reactions within the cell.

The research, entitled "The origin of the electrostatic perturbation in acetoacetate decarboxylase," appears online in Nature. Its authors are Boston University chemistry professor Karen N. Allen, Ph.D., BU graduate student Meng-Chiao Ho and post-doctoral associate Jean-Francois Menetret, and Hiro Tsuruta of the Stanford Synchrotron Radiation Lightsource of the National Accelerator Laboratory.

"Westheimer was right about the enzyme controlling the microenvironment around the reaction, but the way it did it was completely different than he and his research team supposed," said Allen, who named the protein fold she discovered after Westheimer .

Proteins are the biological workhorses that provide the vital functions in every cell. To carry out their tasks, proteins must fold into the complex three dimensional shapes that provide their structure.

"That's the importance of this finding, she added. "Now that we know the structure, we can go back and correct all the text books citing the origin of electrostatic effects in enzyme active sites and say that while the hypothesis was right – and proven for other enzymes -- the basis for it was actually different than what they originally believed."

With a structure fully identified, researchers hope to gain new insights into predicting the functions of other enzymes. The discovery of novel structures also allows researchers to find the active sites and therefore the chemical roles of enzymes of unknown function, uncovering new metabolic pathways in the cell.

An understanding of the molecular detail of an enzyme, like AADase may also enable researchers in protein engineering to alter its structure to work with specific solvents to develop new environmentally friendly "green" biofuels.


Story Source:

The above story is based on materials provided by Boston University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Meng-Chiao Ho, Jean-Franηois Mιnιtret, Hiro Tsuruta, Karen N. Allen. The origin of the electrostatic perturbation in acetoacetate decarboxylase. Nature, 2009; 459 (7245): 393 DOI: 10.1038/nature07938

Cite This Page:

Boston University Medical Center. "Long-awaited Atomic Structure Of Well-known Enzyme Solved: Discovery Heralds New Approaches To Protein-engineered Biofuels." ScienceDaily. ScienceDaily, 21 May 2009. <www.sciencedaily.com/releases/2009/05/090520140401.htm>.
Boston University Medical Center. (2009, May 21). Long-awaited Atomic Structure Of Well-known Enzyme Solved: Discovery Heralds New Approaches To Protein-engineered Biofuels. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2009/05/090520140401.htm
Boston University Medical Center. "Long-awaited Atomic Structure Of Well-known Enzyme Solved: Discovery Heralds New Approaches To Protein-engineered Biofuels." ScienceDaily. www.sciencedaily.com/releases/2009/05/090520140401.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Matter & Energy News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Car Park Solution for Flexible Green Energy

Car Park Solution for Flexible Green Energy

Reuters - Innovations Video Online (Nov. 24, 2014) — A British solar power start-up says that by covering millions of existing car park spaces around the UK with flexible solar panels, the country's power problems could be solved. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Microsoft Adds Robot Guards, Ushers In Sci-Fi Apocalypse

Microsoft Adds Robot Guards, Ushers In Sci-Fi Apocalypse

Newsy (Nov. 23, 2014) — Microsoft has robotic security guards working at its Silicon Valley Campus. Video provided by Newsy
Powered by NewsLook.com
Toyota's Hydrogen Fuel-Cell Green Car Soon Available in the US

Toyota's Hydrogen Fuel-Cell Green Car Soon Available in the US

AFP (Nov. 21, 2014) — Toyota presented its hydrogen fuel-cell compact car called "Mirai" to US consumers at the Los Angeles auto show. The car should go on sale in 2015 for around $60.000. It combines stored hydrogen with oxygen to generate its own power. Duration: 01:18 Video provided by AFP
Powered by NewsLook.com
Google Announces Improvements To Balloon-Borne Wi-Fi Project

Google Announces Improvements To Balloon-Borne Wi-Fi Project

Newsy (Nov. 21, 2014) — In a blog post, Google said its balloons have traveled 3 million kilometers since the start of Project Loon. Video provided by Newsy
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

 

Space & Time

Matter & Energy

Computers & Math

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