Navigation Links
Caught in the act: The dynamic dance of enzymes
Date:12/11/2007

Waltham, MAIn a new study in Nature, Brandeis University Howard Hughes Medical Investigator Dr. Dorothee Kern and collaborators pull back the curtain on the secret lives of enzymes, the ubiquitous proteins that catalyze chemical reactions in the cell. Harnessing a slew of sophisticated technologies to capture a key enzyme changing shape in near real time, Kern was able to show that these proteins are not the wallflowers of the biological world scientists had once thought, essentially passive until catalysis occurs. Rather, Kern and her team demonstrated that the enzyme adenylate kinase, and presumably many more, engages in a dynamic dance even before its catalytic datethe substrate to which it bindsshows up.

If one of the constants of life is change over time, implicit in this truth is how macroscopic change, such as the growth of a child, is ultimately rooted in microscopic change, such as atoms moving in a protein. Kerns study is remarkable in its ability to document the tiny flutterings of enzymes just before they do their all important catalytic work.

In two Nature articles, Kern and collaborators were able, in effect, to create a motion picture of an enzyme as it actually changed shape, or conformations, in the absence of the substrate. Its really a paradigm shift, said Kern. Earlier studies had been able only to create snapshots of enzymes frozen in time, obscuring their true restless, twitching selves.

The three-year study represents a breakthrough in scientific understanding of the dynamic personalities of enzymes. For years, Kern has dedicated herself to capturing how enzymes move and change shape through time. She pioneered the use of nuclear magnetic resonance (NMR), which can detect the motion of individual atoms in a protein, in this biophysical application.

But in this study, Kern, who earlier in life was the point guard on the East German national womens basketball team, knew she had to create a gold-standard strategy that would capture not only the motion of a key protein, but its structures, as well. She had to make sure that the fleeting, more infrequent shapes of enzymes couldnt essentially wiggle out of the picture. These rarer enzyme states are critical to understand, as they are the ones most relevant to better drug design.

Ultimately, Kern harnessed five different elegant techniques, including X-ray crystallography, (NMR), single-molecule fluorescence resonance energy transfer (FRET), computer simulations of molecular dynamics, and paramagnetism, to reveal the full picture of how proteins fold in those infrequent, yet lightening-fast intermediate states between inactivity and activity. Each technique provided a piece of the puzzle.

The big goal here is to understand proteins well enough so that we can actually predict how they will behave, said Kern. These short-lived structures are most likely to have a higher affinity to drug molecules. Instead of relying on trial and error, scientists may be able to rationally design drugs to specifically bind to these intermediate conformations, according to Kern.

With the ability to capture an enzyme in real time as it is moving toward the active state, Kern and co-workers were able to detect picosecond (one millionth of one millionth of a second) changes, the fast smaller conformational motions, as well as the millisecond large-scale motions that are a result of the many fast motions.

This work will lead to understanding the physical nature of proteins not as a static picture but as an ensemble of structures, said Kern.


'/>"/>

Contact: Laura Gardner
gardner@brandeis.edu
781-736-4204
Brandeis University
Source:Eurekalert

Related medicine news :

1. Higher levels of pollutants found in fish caught near a coal-fired power plant
2. Extracts of catfish caught in polluted waters cause breast cancer cells to multiply
3. Dominium Benefits Experiencing Dynamic Growth
4. CardioDynamics Announces Third Quarter 2007 Conference Call and Webcast
5. International Consulting Firm Health Fitness Dynamics Hired to Oversee Springbrook Inns Planned New Spa
6. Dynamic Energy Systems Goes Online and On-Demand
7. Dynamic Files Articles of Merger; Notifies Nasdaq of Merger with GeoPharma
8. Optimal systemic and splanchnic hemodynamic state after living-donor liver transplantation
9. Cardinal Health Reaffirms Fiscal 2008 EPS Guidance, Updates Segment Profit Outlook
10. QMed, Inc. Comments on Estimated 3rd Quarter Results & Medical Expense Ratio; Sets 2008 Revenue Guidance for Medicare SNPs at $88-95 Million
11. Natural Alternatives International, Inc. Announces Late Filing of its Annual Report on Form 10-K, Revenue for Fiscal 2007 and Guidance on First Quarter of Fiscal 2008
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... June 25, 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe ... from the David Geffen School of Medicine at UCLA. He trained in Internal Medicine ... his fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the ...
(Date:6/25/2016)... , ... June 25, 2016 , ... On Friday, June ... a Bronze Wellness at Work award to iHire in recognition of their exemplary accomplishments ... of the 7th annual Maryland Workplace Health & Wellness Symposium at the BWI Marriott ...
(Date:6/24/2016)... ... 2016 , ... A recent article published June 14 on E ... goes on to state that individuals are now more comfortable seeking to undergo not ... as calf and cheek reduction. The Los Angeles area medical group, Beverly Hills Physicians ...
(Date:6/24/2016)... ... June 24, 2016 , ... June 19, 2016 is World Sickle ... chronic pain and the benefits of holistic treatments, Serenity Recovery Center of ... Sickle Cell Disease. , Sickle Cell Disease (SCD) is a disorder of the red ...
(Date:6/24/2016)... ... June 24, 2016 , ... The ... in Dallas that it will receive two significant new grants to support its ... PHA marked its 25th anniversary by recognizing patients, medical professionals and scientists for ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... Dublin ... of the " Global Markets for Spectroscopy Equipment" ... This report focuses on the global ... including its applications in various applications. The report deals ... three main industries: pharmaceutical and biotechnology, food and beverage, ...
(Date:6/24/2016)... -- Dehaier Medical Systems Ltd. (NASDAQ: DHRM ... sells medical devices and wearable sleep respiratory products in ... agreement with Hongyuan Supply Chain Management Co., Ltd. (hereinafter ... 2016, to develop Dehaier,s new Internet medical technology business. ... leverage Hongyuan Supply Chain,s sales platform to reach Dehaier,s ...
(Date:6/24/2016)... , June 24, 2016 ... Market by Type (Standard Pen Needles, Safety Pen Needles), ... (Insulin, GLP-1, Growth Hormone), Mode of Purchase (Retail, Non-Retail) ... MarketsandMarkets, This report studies the market for the forecast ... to reach USD 2.81 Billion by 2021 from USD ...
Breaking Medicine Technology: