Navigation Links
Worth a thousand words: Hopkins researchers paint picture of cancer-promoting culprit
Date:1/4/2008

They say that a picture can be worth a thousand words. This especially is true for describing the structures of molecules that function to promote cancer. Researchers at Johns Hopkins have built a three-dimensional picture of an enzyme often mutated in many types of cancers. The results, published Dec. 14 in Science, suggest how the most common mutations in this enzyme might lead to cancer progression.

Now that we have a better picture of the protein and how it is altered in cancer, we can envision development of mutation-specific inhibitors for cancer therapy, says Victor Velculescu, M.D., Ph.D., associate professor at the Johns Hopkins Kimmel Cancer Center.

The enzyme known as PIK3CA is mutated frequently in many cancers, including colon, brain, stomach, breast and lung. Moreover, most of the reported mutations occur in a few so-called hotspots in the protein. All known mutations make PIK3CA more active than normal, which causes cells to divide more frequently or faster than normal to give rise to cancer.

We tried to guess how the enzymes activity was affected by the mutations based on their locations along the length of the protein, says L. Mario Amzel, Ph.D., professor and director of biophysics and biophysical chemistry at Hopkins. But without a 3-D structure, its hard to do. Its like having a puzzle but missing critical pieces.

The research team isolated purified PIK3CA and part of another protein it normally binds to, grew crystals of the purified enzyme bound to its partner and figured out its 3-D structure using techniques that shoot X-rays through the protein crystals. Using computers, they analyzed the X-ray pattern and assembled a 3-D model of the enzyme. Onto this model the researchers then mapped all the cancer-associated mutations.

According to Sandra Gabelli, Ph.D., an instructor of biophysics and biophysical chemistry at Hopkins, the researchers originally suspected that the mutations somehow interfered with the way PIK3CA interacted with other proteins and parts of the cell and therefore must be on the outside surface of the enzyme. However, their results show that nearly all the mutations map to regions within the enzyme. Somehow, these internal mutations must cause the protein to subtly change how it works and interacts with itself, says Amzel. Its an interesting problem to solve, trying to figure out what slight shape and structural changes can make an enzyme work better-usually were trying to figure out why things stop working.

The team currently is unraveling the structure of mutated PIK3CA so that they can compare mutated to unmutated to better understand how the mutations lead to cancer. Another goal is to find drugs that can specifically interfere with PIK3CA and turn it down, to develop cancer-fighting therapies.


'/>"/>

Contact: Audrey Huang
audrey@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
Source:Eurekalert

Related biology news :

1. Thousands of starving children could be restored to health with peanut butter program
2. How mother of thousands makes plantlets
3. Vaginal reconstruction not needed for most inter-sex females, Hopkins study shows
4. Researchers identify proteins involved in new neurodegenerative syndrome
5. Texas researchers and educators head for Antarctica
6. MGH researchers describe new way to identify, evolve novel enzymes
7. University of Pennsylvania researchers develop formula to gauge risk of disease clusters
8. U of MN researchers discover noninvasive diagnostic tool for brain diseases
9. U of Minnesota researchers discover noninvasive diagnostic tool for brain diseases
10. Researchers discover new strategies for antibiotic resistance
11. Researchers find new taste in fruit flies: carbonated water
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/15/2016)... CHICAGO , April 15, 2016  A ... companies make more accurate underwriting decisions in a ... offering timely, competitively priced and high-value life insurance ... health screenings. With Force Diagnostics, rapid ... and lifestyle data readings (blood pressure, weight, pulse, ...
(Date:4/13/2016)... , April 13, 2016  IMPOWER physicians supporting ... are setting a new clinical standard in telehealth thanks ... By leveraging the higi platform, IMPOWER patients can routinely ... pulse and body mass index, and, when they opt ... and convenient visit to a local retail location at ...
(Date:3/29/2016)... 29, 2016 LegacyXChange, Inc. (OTC: ... and SelectaDNA/CSI Protect are pleased to announce our successful ... a variety of writing instruments, ensuring athletes signatures against ... collectibles from athletes on LegacyXChange will be assured of ... DNA. Bill Bollander , CEO states, ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... 23, 2016 , ... UAS LifeSciences, one of the leading ... UP4™ Probiotics, into Target stores nationwide. The company, which has been manufacturing high ... its list of well-respected retailers. This list includes such fine stores as Whole ...
(Date:6/23/2016)... , June 23, 2016 /PRNewswire/ - FACIT has ... Ontario biotechnology company, Propellon Therapeutics Inc. ... and commercialization of a portfolio of first-in-class WDR5 ... targets such as WDR5 represent an exciting class ... in precision medicine for cancer patients. Substantial advances ...
(Date:6/23/2016)... , June 23, 2016 Houston ... with the Cy-Fair Sports Association to serve as ... the agreement, Houston Methodist Willowbrook will provide sponsorship ... and connectivity with association coaches, volunteers, athletes and ... with the Cy-Fair Sports Association and to bring ...
(Date:6/23/2016)... June 23, 2016  The Prostate Cancer Foundation (PCF) is pleased ... and faster cures for prostate cancer. Members of the Class of 2016 were ... Read More About the Class of 2016 PCF Young ... ... ...
Breaking Biology Technology: