Navigation Links
Is it a rock, or is it Jell-O? Defining the architecture of rhomboid enzymes
Date:8/2/2012

Johns Hopkins scientists have decoded for the first time the "stability blueprint" of an enzyme that resides in a cell's membrane, mapping which parts of the enzyme are important for its shape and function. These studies, published in advance online on June 14 in Structure and on July 15 in Nature Chemical Biology, could eventually lead to the development of drugs to treat malaria and other parasitic diseases.

"[It's] the first time we really understand the architectural logic behind the structure of the enzyme," says Sinisa Urban, Ph.D., an associate professor of molecular biology and genetics at the Johns Hopkins University School of Medicine and an investigator at the Howard Hughes Medical Institute, who with his team has unlocked the mysteries of a special class of enzymes called rhomboid proteases.

Rhomboid proteases are present in many different organisms, and are a unique type of enzyme that resides in the cell's membrane where they cut proteins. Previously Urban and his colleagues demonstrated that the rhomboid enzyme is critical for Plasmodium falciparum, the parasite that causes malaria, to successfully invade red blood cells, a step that ultimately leads to infection. Urban says understanding the stability of rhomboid protease shape may impact the design of enzyme inhibitors potential drugs. "These enzymes have no selective inhibitors," says Urban. "We really need to understand how [the enzyme] works is it as stiff as a rock, or is it more gummy, like Jell-O?"

One challenge of studying rhomboid enzymes is that they are surrounded by membranes, making them more difficult to manipulate and work with. To address this, Urban's research team turned to a technique known as thermal light scattering, which heats enzyme samples to progressively higher temperatures while measuring the amount of light bouncing back off of the molecules. Enzymes that have broken from their normal shape will scatter light differently, and the temperature at which this occurs (in effect, the breaking point of the enzyme) indicates the inherent stability of the enzyme.

The researchers first precisely measured the stability of the rhomboid enzyme from E. coli bacteria. Surprisingly, says Urban, the rhomboid enzyme was more "Jell-O-like" than other membrane proteins with similar shapes. He guesses that this "jiggly shape" may help rhomboid proteases interact with other proteins that it cuts. To find which parts of the enzyme are most important for maintaining shape and which parts are more crucial for function, the researchers then made and tested 150 differently altered versions of the enzyme. They found four main regions important for maintaining shape and at least two regions important for function.

The researchers also took advantage of computer simulations to test their ideas about how the enzyme functions. Using a computer program model of the enzyme, they programmed in features of its natural membrane environment, which consists mostly of fats and is very limited in water. The computer program then simulated how this environment might influence the enzyme. Researchers found that the enzyme contains a special internal pocket for holding water molecules a great advantage in its natural, water-limiting environment.

"We're very excited about our findings and are especially curious about the versions of the enzyme that lost function despite no obvious change in stability or shape," says Urban. Ultimately he hopes that a better understanding of rhomboid proteases will lead to new therapies for treating malaria and other parasitic diseases.


'/>"/>
Contact: Vanessa McMains
vmcmain1@jhmi.edu
410-502-9410
Johns Hopkins Medical Institutions
Source:Eurekalert  

Related biology news :

1. Force of nature: Defining the mechanical mechanisms in living cells
2. Herbivores select on floral architecture in a South African bird-pollinated plant
3. ORNL process improves catalytic rate of enzymes by 3,000 percent
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Is it a rock, or is it Jell-O? Defining the architecture of rhomboid enzymes
(Date:5/6/2017)... , May 5, 2017 ... just announced a new breakthrough in biometric authentication ... exploits quantum mechanical properties to perform biometric authentication. These ... smart semiconductor material created by Ram Group and ... finance, entertainment, transportation, supply chains and security. Ram ...
(Date:4/17/2017)... April 17, 2017 NXT-ID, Inc. (NASDAQ: ... the filing of its 2016 Annual Report on Form 10-K on ... ... is available in the Investor Relations section of the Company,s website ... SEC,s website at http://www.sec.gov . 2016 Year Highlights: ...
(Date:4/11/2017)... , Apr. 11, 2017 Research and Markets ... 2017-2021" report to their offering. ... The global eye tracking market to grow at a CAGR ... Global Eye Tracking Market 2017-2021, has been prepared based on an ... the market landscape and its growth prospects over the coming years. ...
Breaking Biology News(10 mins):
(Date:10/10/2017)... ... October 10, 2017 , ... ... advancing targeted antibody-drug conjugate (ADC) therapeutics, today confirmed licensing rights that give ... Liposomal Nanoparticle), a technology developed in collaboration with Children’s Hospital Los Angeles ...
(Date:10/10/2017)... SANTA BARBARA, CALIFORNIA (PRWEB) , ... October 10, ... ... risk management, technological innovation and business process optimization firm for the life sciences ... the BoxWorks conference in San Francisco. , The presentation, “Automating GxP ...
(Date:10/9/2017)... ... October 09, 2017 , ... The Giving Tree Wellness ... targeting the needs of consumers who are incorporating medical marijuana into their wellness ... Arizona. , As operators of two successful Valley dispensaries, The Giving Tree’s two ...
(Date:10/6/2017)... ... October 06, 2017 , ... The ... and technology sector at their fourth annual Conference where founders, investors, innovative practitioners ... and the ELEVATE pitch competition showcasing early stage digital health and med tech ...
Breaking Biology Technology: