Featured Research

from universities, journals, and other organizations

Hidden protein structures are essential for catalysis

Date:
December 3, 2009
Source:
Brandeis University
Summary:
A new study raises the curtain on the hidden lives of proteins at the atomic level. The study reports that for the first time, researchers used x-ray crystallography and nuclear magnetic resonance (NMR) techniques to directly visualize protein structures essential for catalysis at the rare high-energy state. The study also showed how the motions of these rare, or hidden, structures collectively, directly contribute to enzyme catalysis.

The hidden alternate structure of the human prolyl isomerase uncovered by ambient temperature high-resolution x-ray crystallography. Fast flipping between the main (blue) and minor (light blue) structures is essential for catalytic power.
Credit: Dorothee Kern

An important Brandeis study appearing in the December 3 issue of Nature raises the curtain on the hidden lives of proteins at the atomic level. The study reports that for the first time, researchers used x-ray crystallography and nuclear magnetic resonance (NMR) techniques to directly visualize protein structures essential for catalysis at the rare high-energy state. The study also showed how the motions of these rare, or hidden, structures collectively, directly contribute to enzyme catalysis.

In doing so, the study also suggests new molecular sites for potential drug targets, the cornerstone of rational drug design. Drugs may bind, or dock, to the infrequent high-energy states of target enzymes that have been hidden to traditional structural methods. The thinking is that drugs can be designed by docking algorithms to a collection of protein structures, not just one, providing better bio-molecular targeting.

This study comes in the wake of earlier Brandeis studies aimed at advancing understanding of protein function using pioneering techniques such as NMR. For a long time, scientists viewed proteins more or less as macromolecular wallflowers, venturing out onto the atomic-level dance floor to perform only during catalysis, their active state.

Then, several years ago, Brandeis biophysicist Dorothee Kern reported in Nature that her lab's experiments using NMR also linked protein function to their much rarer high-energy state, in the absence of catalysis. That study helped put to rest the conventional wisdom that proteins actually rest at all.

This Nature study takes Kern's research to the next level, seeing the high-resolution structure of the hidden, high-energy state for the first time. For this success, high -resolution x-ray crystallography was further pushed by analyzing electron density data previously discarded as "noise" and by collecting data at ambient temperature. The protein of interest is human cyclophilin A, an enzyme that is highjacked by the HIV virus to aid its own replication.

But it was thanks to some clever protein design together with dynamic NMR spectroscopy that provided direct experimental evidence that the hidden structures in the high-energy state are in fact essential for catalysis. The researchers revealed what happens when proteins flip from the rare state to a major state in a process called interconversion. If this flip is fast, then the enzyme does its job fast, but if the flip is slow, as in the designer enzyme, then the enzyme operates slowly.

"People always focused on the chemistry -- accelerating the reaction through catalyzing the chemical step of the substrates. What we've shown is that protein dynamics is as important as the chemical step," said Kern, a Howard Hughes Medical Institute Investigator. "Basically, all the steps need to be choreographed just right, like steps for a beautiful dancer. An enzyme can only function well with the perfect choreography of all the components."

Said Kern: "We now can show directly that the higher energy states are always there and that these hidden, rare states are absolutely essential for protein function."


Story Source:

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


Cite This Page:

Brandeis University. "Hidden protein structures are essential for catalysis." ScienceDaily. ScienceDaily, 3 December 2009. <www.sciencedaily.com/releases/2009/12/091202131624.htm>.
Brandeis University. (2009, December 3). Hidden protein structures are essential for catalysis. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2009/12/091202131624.htm
Brandeis University. "Hidden protein structures are essential for catalysis." ScienceDaily. www.sciencedaily.com/releases/2009/12/091202131624.htm (accessed July 23, 2014).

Share This




More Matter & Energy News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Boeing Ups Outlook on 52% Profit Jump

Boeing Ups Outlook on 52% Profit Jump

Reuters - Business Video Online (July 23, 2014) Commercial aircraft deliveries rose seven percent at Boeing, prompting the aerospace company to boost full-year profit guidance- though quarterly revenues missed analyst estimates. Bobbi Rebell reports. Video provided by Reuters
Powered by NewsLook.com
Europe's Car Market on the Rebound?

Europe's Car Market on the Rebound?

Reuters - Business Video Online (July 23, 2014) Daimler kicks off a round of second-quarter earnings results from Europe's top carmakers with a healthy set of numbers - prompting hopes that stronger sales in Europe will counter weakness in emerging markets. Hayley Platt reports. Video provided by Reuters
Powered by NewsLook.com
9/11 Commission Members Warn of Terror "fatigue" Among American Public

9/11 Commission Members Warn of Terror "fatigue" Among American Public

Reuters - US Online Video (July 22, 2014) Ten years after releasing its initial report, members of the 9/11 Commission warn of the "waning sense of urgency" in combating terrorists attacks. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Government Approves East Coast Oil Exploration

Government Approves East Coast Oil Exploration

AP (July 18, 2014) The Obama administration approved the use of sonic cannons to discover deposits under the ocean floor by shooting sound waves 100 times louder than a jet engine through waters shared by endangered whales and turtles. (July 18) Video provided by AP
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:
from the past week

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