Navigation Links
CSHL structural biologists reveal novel drug binding site in NMDA receptor subunit
Date:6/16/2011

Structural biologists at Cold Spring Harbor Laboratory (CSHL) have obtained a precise molecular map of the binding site for an allosteric inhibitor in a subtype of the NMDA (N-methyl-D-aspartate) receptor, which is commonly expressed in brain cells.

The newly discovered binding site -- a docking port within the receptor -- is important because it is a potential target for drugs that can modulate NMDA receptors, dysfunctions of which have been implicated in depression, schizophrenia, Parkinson's and Alzheimer's diseases as well as stroke-related brain injuries.

Allosteric sites in neurotransmitters are distinguished from their "primary" or "active" binding sites. Importantly, the newly obtained molecular map will enable scientists to design highly specific compounds that home in on the allosteric site, thereby minimizing "off-target effects," which give rise to a drug's unwanted side effects.

In a study led by CSHL Associate Professor Hiro Furukawa and published June 15 in the journal Nature, the allosteric site of interest is shown to be in the region of NMDA receptors called the amino terminal domain. A class of allosteric inhibitors for NMDA receptors, called phenylethanolamines, has previously been identified. One such compound, ifenprodil, is known to bind specifically to the GluN1/GluN2B subtype of the NMDA receptor, but not to other subtypes. The neuroprotective properties of phenylethanolamines have inspired scientists to employ them for treatment of neurological diseases and disorders. Some are now being tested in clinical trials for depression, pain, Parkinson's disease, and Alzheimer's disease.

The detailed blueprint of the allosteric site where phenylethanolamines bind to the receptor will facilitate rational design of improved compounds. In the work published on June 15th, Furukawa's group identifies the precise binding site of phenylethanolamine within the amino terminal domain of GluN1/GluN2B NMDA receptors. The results were obtained through biochemistry and x-ray crystallography, a method that features exposing a crystalline form of the molecule under study to very high-energy x-ray beams, which reveals its features in great detail. This enabled the team to demonstrate that phenylethanolamine is recognized at the interface of the GluN1 and GluN2B subunits of the receptor, rather than at a previously predicted site within GluN2B.

"Before this study, we did not have a sufficiently precise map of NMDA receptor subunits to facilitate the design of better and more effective compounds that could dock at the allosteric site. Our results should move drug development in the right direction. We are now optimistic that the field can determine optimal ways of targeting NMDA receptors for therapeutic purposes," Furukawa says.


'/>"/>

Contact: Peter Tarr
tarr@cshl.edu
516-367-5055
Cold Spring Harbor Laboratory
Source:Eurekalert

Related medicine news :

1. Current opinion in structural biology and DNA repair
2. Learning causes structural changes in affected neurons
3. Study finds structural brain alterations in patients with irritable bowel syndrome
4. Mount Sinai researchers find structural basis for incidence of skin cancers in a genetic disorder
5. Childhood stress such as abuse or emotional neglect can result in structural brain changes
6. Tufts biologists find another clue to the origins of degenerative diseases
7. MIT biologists pinpoint a genetic change that helps tumors move to other parts of the body
8. Biologists discover control center for sperm production
9. National Academy of Sciences honors microbiologists for major scientific contributions
10. Biologists, educators recognize excellence in evolution education
11. Caltech biologists discover microRNAs that control function of blood stem cells
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/18/2017)... Fresno, CA (PRWEB) , ... January 18, 2017 ... ... is pleased to announce that their Vice President of Franchise Development, Paula Turner ... , This award-winning business program, which features the insights of top business leaders ...
(Date:1/18/2017)... ... ... At Hallmark Nameplate, their commitment to quality is what sets them apart. The ... certification is another way they are making constant strides to provide all customers with ... The ISO 13485 Certification is a major accomplishment for Hallmark Nameplate and will allow ...
(Date:1/18/2017)... ... 18, 2017 , ... Michael J. Hennessy Associates, Inc., (MJH), ... for Biosimilars, announced Michael J. Hennessy Associates, Inc. President Michael J. Hennessy, Jr. ... through thought leader interaction in, live video and interactive digital platforms. , In ...
(Date:1/18/2017)... Hills, CA (PRWEB) , ... January 18, 2017 ... ... of dental problems ranging from gum disease to enamel erosion, and those dental ... the Massachusetts Department of Public Health, many pregnant women are failing to get ...
(Date:1/17/2017)... , ... January 17, 2017 , ... Anesthesia Progress ... for dentists to choose the best drug option for each patient. Dentists have several ... and better overall outcomes. , Researchers from the Tokyo Dental College in Tokyo, Japan ...
Breaking Medicine News(10 mins):
(Date:1/19/2017)... 2017  ViewRay, Inc. (Nasdaq: VRAY ... clinical MRI-guided radiation therapy system, announced today that it ... million through a private placement of its common ... financing and was joined by certain of ViewRay,s ... Venture Partners, and an additional new institutional investor, ...
(Date:1/19/2017)... Jan. 18, 2017 The drug delivery technology ... 2021 from USD 1,179.20 billion in 2016, at a ... prevalence of chronic diseases, increasing demand for biologics, technological ... the growth of this market. Whereas, self-administration & home ... offer significant growth opportunities for players operating in this ...
(Date:1/18/2017)... 18, 2017  Aprima Medical Software, a leading ... management (PM) and revenue cycle management (RCM) solutions ... a former reseller Healthcare Data Solutions (HDS) of ... Aprima will assume full support for HDS,s customers, ... practices across 15 states. Financial terms were not ...
Breaking Medicine Technology: