Navigation Links
Researchers unveil vital key to cancer
Date:8/6/2008

Mps1 belongs to the family of proteins called kinases. When subsets of these enzymes become deregulated, cancer can be one of the outcomes making them a critical target for research by oncologists. Over 100 of the 500 or so kinases have been shown to be associated with cancer, but so far scientists only know the 3D structure of a handful. Knowing the structure is critical for the design of new kinase inhibitors as therapeutic agents, an area of enormous importance to the pharmaceutical industry. Over 100 kinase inhibitors are currently in clinical trials, and the revolutionary kinase inhibitor Glivec was approved for treating Leukaemia in the UK in 2001.

Mps1 is particularly important as it controls a 'checkpoint' that cells use to encourage accurate chromosome sorting during mitosis. Mps1 therefore prevents aneuploidy, the change in the number of chromosomes that is closely associated with cancer.

Dr Patrick Eyers and his team, including Hong Kong-born PhD student Matthew Chu, used the Diamond Light synchrotron, a "super-microscope" that works by speeding electrons around a huge doughnut-shaped chamber the size of five football pitches until they are travelling so fast they emit high energy particles. The X-rays were "fired" at a pure sample of the protein, allowing the researchers to "see" the protein's atomic structure for the first time.

Their structure revealed the pocket where Mps1 binds to ATP, the natural substrate from which Mps1 transfers a phosphate group to its cellular target proteins. Further work showed the protein in complex with the ATP-competitive inhibitor SP600125, a well-known but non-specific inhibitor of many kinases, which revealed a secondary pocket not utilised by this compound. If a next-generation drug can be designed to specifically block this secondary pocket, it is hoped that Mps1 will be specifically disabled, killing rapidly dividing cells such as those found in tumours.

The team hopes its work will allow chemists to design an anti-cancer drug with fewer side effects, allowing scientists to assess the relative importance of Mps1 inhibition in different disease indications, including those that are currently hard to treat such as lung and pancreatic cancers.

Dr Eyers, whose findings are published in the Journal of Biological Chemistry (August 2008), said: "The crystallalographic structures of only a few key "mitotic" kinases are currently known so we are very early in the game. The scientific community has high hopes for developing novel "anti-mitotic" cancer therapies using this method of structure-based drug design.

"Mps1 is a rational target because of its critical role in preventing aneuploidy. We wanted to see what this protein looked like at the molecular level and, by revealing the active site "lock", help design a new inhibitory "key" to physically block the ATP-binding site.

His colleague Dr Lydia Tabernero added: "This work presents the first crystallographic structure of human Mps1, an important regulator of chromosomal stability and a potential target in cancer therapy. Our research has revealed several important structural features and additional binding sites that could be exploited for the development of specific Mps1 inhibitors."


'/>"/>

Contact: Mikaela Sitford
Mikaela.Sitford@manchester.ac.uk
01-612-752-111
University of Manchester
Source:Eurekalert

Related medicine news :

1. Stanford researchers find culprit in aging muscles that heal poorly
2. UCLA researchers identify markers that may predict diabetes in still-healthy people
3. Mayo Clinic researchers discover new diagnostic test for detecting infection in prosthetic joints
4. Bipolar disorder relapses halved by Melbourne researchers
5. Cell that triggers symptoms in allergy attacks can also limit damage, Stanford researchers find
6. High and mighty: first common height gene identified by researchers behind obesity gene finding
7. Researchers estimate about 9 percent of US children age 8 to 15 meet criteria for having ADHD
8. Majority of 2.4 Million U.S. Children With ADHD Not Diagnosed or Consistently Treated, According to New Gold Standard Study by Cincinnati Childrens Researchers
9. Researchers develop long-lasting growth hormone
10. Jefferson immunology researchers halt lethal rabies infection in brain
11. Purdue researchers develop technology to detect cancer by scanning surface veins
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/29/2016)... ... , ... Our bodies are bombarded daily by environmental and lifestyle factors that ... is to adopt a more healthful diet, but too many people think that food ... Nutritionist and the creator of the Newport Beach Cleanse and 14-Day Eating Plan, disagrees ...
(Date:4/29/2016)... , ... April 29, 2016 , ... On Tuesday, April ... across the Southeast, celebrated the signature of Gov. Nathan Deal on SB 258, the ... Duncan (R - Cumming), offers a 70% tax credit to individuals and corporations which ...
(Date:4/29/2016)... ... April 29, 2016 , ... The American workforce ... stability, even security. Most importantly, employees are the single most important asset in ... workers so unhappy? , Just under half of American workers are emotionally checked ...
(Date:4/29/2016)... ... April 29, 2016 , ... Dr. Bernie Siegel, ... "LOVE, MEDICINE and MIRACLES") addresses touchy topics related to Death live on ... Dr. Bernie Siegel, author of a plethora of essential books-to-read for physicians ...
(Date:4/29/2016)... ... April 29, 2016 , ... The White House ... their loans, more information about their loan terms and accounts, and more protections ... debt, including federal and private loans, has reached $1.3 trillion, with 43 million ...
Breaking Medicine News(10 mins):
(Date:4/29/2016)... BERLIN , April 29, 2016 ... world-leading glyco-biology expertise, today announces the appointment of Dr. ... Dr. Zurlo is an oncologist with many years ... pharmaceutical and biotechnology industries. His last role was at ... Member of the Executive Board. Previously Dr. Zurlo held ...
(Date:4/28/2016)... 2016  Marking its one year anniversary since ... cancer risk test, Color Genomics announced ... highly impact the most common hereditary cancers affecting ... Test analyzes hereditary cancer risks for breast, colorectal, ... The Color Test is physician ordered and includes ...
(Date:4/28/2016)... , April 28, 2016 Dr. ... and Ste phen ... ArisGlobal®, a leading provider of cloud-based software solutions for life ... Pharmacovigilance team to bring a wealth of insight to a growing ... pharmacovigilance knowledge. George Phillips joined ArisGlobal in ...
Breaking Medicine Technology: