Navigation Links
Study details structure of potential target for HIV and cancer drugs
Date:10/7/2010

In a technical tour de force, structural biologists funded by the National Institutes of Health have determined the three-dimensional structure of a molecule involved in HIV infection and in many forms of cancer. The high-resolution structure sheds light on how the molecule functions and could point to ways to control its activity, potentially locking out HIV and stalling cancer's spread.

The molecule, CXCR4, is part of a large family of proteins called G-protein coupled receptors (GPCRs). These molecules span the cell's membrane and transmit signals from the external environment to the cell's interior. GPCRs help control practically every bodily process, including cell growth, hormone secretion and light perception. Nearly half of all drugs on the market target these receptors.

"Scientists have been studying CXCR4 for years but have only been able to guess at what it looks like," said NIH Director Francis S. Collins, M.D., Ph.D. "Now that we have its structure, we have a much clearer picture of how this medically important molecule works, opening up entire new areas for drug discovery."

The researchers, led by Raymond C. Stevens, Ph.D., of the Scripps Research Institute in La Jolla, Calif., report their findings in the Oct. 7, 2010, advance online issue of the journal Science. The study received support from two major NIH initiatives: the structural biology program of the NIH Common Fund and the Protein Structure Initiative (PSI).

While a molecule called CD4 is the primary receptor for HIV, CD4 is not sufficient for the virus to penetrate cells. In 1996, a team of researchers at NIH's National Institute of Allergy and Infectious Diseases (NIAID) discovered that CXCR4 acts as a co-receptor by helping HIV enter cells.

Normally, CXCR4 helps activate the immune system and stimulate cell movement. But when the signals that activate the receptor aren't properly regulated, CXCR4 can spur the growth and spread of cancer cells. To date, CXCR4 has been linked to more than 20 types of cancer.

The Scripps Research scientists set out to shed light on how CXCR4 functions by capturing snapshots of the protein by using a structure determination method called X-ray crystallography. To understand how natural molecules might bind and signal through the receptor and to see how potential drugs could interact with it, they examined CXCR4 bound to known inhibitors of its activity.

Determining the structure of CXCR4 represented a major challenge because membrane proteins are notoriously tricky to coax into the crystal form required for the X-ray technique. After three years of optimizing conditions for producing, stabilizing and crystallizing the molecule, the scientists finally generated five distinct structures of CXCR4.

The structures showed that CXCR4 molecules form closely linked pairs, confirming data from other experiments indicating that pairing plays a role in the proper functioning of the receptor. With this knowledge, scientists can delve into how the duos might regulate CXCR4's activity and better understand how CXCR4 functions under normal and disease conditions.

The images also showed that CXCR4 is shaped like two white wine glasses touching in a toast, with the inhibitors bound at the sides of the bowls. By detailing these contacts, the researchers said the pictures suggest how to design compounds that regulate CXCR4 activity or block HIV entry into cells. If developed into drugs, such compounds could offer new ways to treat HIV infection or cancer.

"An approach to determining protein structures that was developed with support from the NIH Common Fund and the PSI is now paying huge dividends," said Jeremy M. Berg, Ph.D., director of the National Institute of General Medical Sciences, which supports the PSI. "It illustrates how technical progress provides a foundation for rapid advances, and it also showcases the benefits of collaborations between structural biologists and scientists working in other fields for addressing fundamentally important problems with tremendous potential for medical applications."


'/>"/>

Contact: Emily Carlson
carlsone@nigms.nih.gov
301-496-7301
NIH/National Institute of General Medical Sciences
Source:Eurekalert  

Related medicine news :

1. Denser Breasts Raise Odds of Second Breast Cancer, Study Finds
2. U-M receives NIH, FDA grant to study adaptive clinical trial designs
3. Stanford-led study disproves link between genetic variant, risk of coronary artery disease
4. Study shows faith-based interventions can encourage exercise in older African-American women
5. Study links large waist size to higher diabetes rates among Americans
6. Drink or Two a Week While Pregnant Might Not Harm Baby: Study
7. Provocative new Montreal study probes link between breast cancer and air pollution
8. UF study: Emotional effects of heavy combat can be lifelong for veterans
9. MFM researcher earns $3.7M NIH grant to study preterm birth
10. New study highlights sexual behavior, condom use by US individuals ages 14 to 94
11. Study focuses on mephedrone use in Northern Ireland post-ban
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Study details structure of potential target for HIV and cancer drugs
(Date:2/13/2016)... ... February 13, 2016 , ... The producers of Enterprises TV ... , The increasingly modern world of instantaneous consumption proves very convenient for businesses. ... such as oil and coal, which pollutes our air, water, and soil. It can ...
(Date:2/13/2016)... , ... February 13, 2016 , ... ... Outlook’s top Clinical Data Management Solution Providers list for its expertise in eClinical ... and domain expertise to serve the technology needs of global clients. DDi provides ...
(Date:2/12/2016)... ... February 12, 2016 , ... ... exclusively to funding innovative lymphoma research and serving the lymphoma community through a ... 250 members of South Florida’s philanthropic community at its 10th anniversary Fashion Luncheon ...
(Date:2/12/2016)... ... ... Coco Libre, the maker of coconut water beverages with a purpose, is ... Coco Libre will offer musicians and celebrities the company’s signature Organic Coconut Water, a ... suite, held this year at the W Hollywood Hotel, has become a pre-show “must” ...
(Date:2/12/2016)... (PRWEB) , ... February 12, 2016 , ... Fisher House ... Vegas Mayor John J. Lee, Nevada Military Support Alliance president Scott Bensing, and Peggy ... at the VA Southern Nevada Healthcare System. This will be the first Fisher ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)... 2016 The primary goal of this research ... on the usage of liquid biopsy. Key information the ... - Timeframe of liquid biopsy adoption amidst future users ... organization type - Sample inflow to conduct liquid biopsy ... serum, and so on. - Correlation analysis of sample ...
(Date:2/11/2016)... 11, 2016 PRO-DEX, INC. (NasdaqCM: PDEX) today announced ... 31, 2015. The Company also filed its Quarterly Report on ... with the Securities and Exchange Commission today. ... --> --> Net sales ... million, or 95%, to $5.4 million from $2.8 million for ...
(Date:2/11/2016)... -- Kindred Biosciences, Inc. (NASDAQ: KIN ), a biopharmaceutical ... pets, today announced the submission to FDA of the ... (NADA) for Zimeta™ (dipyrone injection, KIND-012).  Positive topline results ... the control of pyrexia (fever) in horses were recently ... --> The Chemistry, Manufacturing, and Controls technical ...
Breaking Medicine Technology: