Navigation Links
Translating Structure into Function

Scientists have perfected ways to determine the knot-like structure of enzymes, but theyve been stumped trying to translate the structure into an understanding of function what the enzyme actually does in the body.

This puzzle has hindered drug discovery, since many of the most successful drugs work by blocking enzyme action. Now, in an expedited article in NATURE, researchers show that a solution to the puzzle is finally in sight.

A team co-led by UCSFs Brian Shoichet, Steven Almo of the Albert Einstein College of Medicine, and Frank Raushel of Texas A&M describes the first success decrypting an enzymes function from its structure. If their new strategy works with other enzymes, it should become a potent tool to determine how key enzymes work in the body.

And since enzyme action is crucial to disease, the technique opens an efficient route to drug discovery, Shoichet say. Schoichet a professor of pharmaceutical chemistry and an investigator in the California Institute for Quantitative Biomedical Research, or QB3, based at UCSF.

The teams success came by modifying a technique called molecular docking, a computer-aided modeling strategy used to search for potential drugs. Docking works by allowing researchers to first determine the atom-by-atom structure of an enzyme and then screen many thousands of molecules for one that fits into the empty active site of the enzyme.

Shoichet calls this a search for the missing piece of a jigsaw puzzle. A molecule that fits the enzymes active site will block its activity just what many promising drugs do.

The strategy works well for one kind of drug discovery -- finding molecules to fit in the active site and physically block enzyme action. But the research team sought to divine from an enzymes structure just what natural molecule triggers the enzyme into action -- fitting into the active site and enabling the enzyme to act as a catalyst.

This wa s a search for the so-called substrate for the enzyme, a search that has never succeeded simply from knowing an enzymes configuration. The key to the teams success was a computational feat: simulating candidate substrates that mimicked unstable intermediate molecules those that exist only briefly as the catalyst turns the substrate into a new molecule.

Because these intermediates are unstable, scientists have until now been unable to test their fit to the enzymes active site.

Once the scientists had predicted the substrate, Raushel, a professor of chemistry at Texas A&M University, tested the prediction experimentally. The results confirmed the prediction. Almo, a professor of biochemistry at Albert Einstein College of Medicine, further confirmed the finding by determining the substrates atomic level structure through x-ray crystallography.

To tell the truth, we were very surprised that the docking approach worked to determine the substrate, says Shoichet. Theres so many ways that the approach can go wrong. Were all very gratified.

For their experiments, the team extracted an enzyme from a bacterium known as Thermotoga maritima, a microbe that normally lives at very high temperatures and pressures near volcanic ocean vents. Its structure was determined as a part of the structural genomics project, a large-scale, worldwide effort to determine the structures of enzymes and receptors.

With the nature of the substrate in hand, the scientists went on to discover that the enzyme works in a previously uncharacterized metabolic pathway in bacteria.


'"/>




Related medicine news :

1. Relationship Between Genetic Structure And Quality of Life
2. Abnormal Brain Structure One Of The Reasons For Depression in Adolescents
3. Structure of the brain to increase risk for anxiety disorders
4. Changes In Brain Structure From Methamphetamine Abuse And HIV Infection
5. Almond Structure in the Brain Intrigues Researchers
6. Controversy over Fees Structure in Private Medical Colleges
7. Controversy Over The Fee Structure In Private Medical Colleges Surfaces Yet Again
8. Education Structure In Indian Schools To Be Revamped Soon
9. Neither Management Nor Students Happy With New Fee Structure
10. DNA-bound p53 Tumor Suppressor Protein Structure Determined
11. Structure of DNA-modifying enzyme In Small Pox Determined
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:12/2/2016)... ... December 02, 2016 , ... More than half of ... 84 percent of parents report speaking with their child about sex related topics, less ... diseases. , Mediaplanet is proud to announce the launch of its second edition of ...
(Date:12/2/2016)... ... December 02, 2016 , ... Sourced from the Isbre Springs beneath the ... its unmatched natural purity of just 6 ppm TDS (Total Dissolved Solids) in addition ... has been available in several ShopRite and FoodTown stores in NJ and received rave ...
(Date:12/2/2016)... ... December 02, 2016 , ... ... to needy individuals and families from eight different sites throughout Miami-Dade and Broward ... Over 1,000 volunteers worked very hard on Thanksgiving morning by putting together individual ...
(Date:11/30/2016)... ... 30, 2016 , ... Northridge dentists, Dr. Assili ... for all patients. Understanding that budget can play a part in oral health ... perks, including discounts on many valuable dental treatments. Options for individuals, couples, and ...
(Date:11/30/2016)... ... November 30, 2016 , ... ... have been a focus of public policymakers and system stakeholders in many states. ... released its Medical Price Index for Workers’ Compensation, Eighth Edition (MPI-WC) . ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... Dec. 2, 2016  The Addiction Treatment Advisory ... of Managed Care Pharmacy (AMCP), has released detailed ... address the opioid addiction crisis, including through improved ... ATAG,s newly released paper, "The Role ... Naloxone," addresses many issues around gaps and barriers ...
(Date:12/2/2016)...  Maxor National Pharmacy Services, LLC ("Maxor"), today announced that ... The combination of Texas -based Maxor Specialty ... bring together both company,s clinical expertise and high-touch patient service ... specialty pharmacy. About Maxor ... , , ...
(Date:12/2/2016)... -- CVS Health Corporation (NYSE: CVS ) ... December 15, 2016, beginning at 8:00 a.m. (ET). Senior members ... in-depth review of the company,s strategies to drive long-term ... discuss 2017 earnings guidance during the event. ... be broadcast simultaneously on the Investor Relations portion of ...
Breaking Medicine Technology: