Breaking News
February 21, 2019 - Mayo clinic researchers discuss local case studies of leprosy
February 21, 2019 - Scientists demonstrate key role of salt in allergic immune reactions
February 21, 2019 - Experts propose revising the criteria for diagnosis of Parkinson’s disease
February 21, 2019 - The med student and the machine
February 21, 2019 - Hey, Hey! Ho, Ho! Is Striking For School Nurses The Way To Go?
February 21, 2019 - Latest research encourages children to move out and learn through physical activity
February 21, 2019 - Proper oral hygiene and regular visits to dentist can promote heart health
February 21, 2019 - New, versatile technique for remote control of transplanted cells in Parkinson’s
February 21, 2019 - Why melanoma tumors in the brain may be worse?
February 21, 2019 - New project aims to improve lung disease care in Appalachia
February 21, 2019 - Drug increases melanin production in some people with albinism
February 21, 2019 - Over 1 in 3 adults miss the mark on protein, finds study
February 21, 2019 - CymaBay Therapeutics Announces Seladelpar Granted Breakthrough Therapy Designation by the FDA for the Treatment of Primary Biliary Cholangitis
February 21, 2019 - A correlation between obesity and income has only developed in the past 30 years
February 21, 2019 - Baby, then work: An effort to help resident-parents in emergency medicine
February 21, 2019 - Heavy cigarette smoking could damage vision, say researchers
February 21, 2019 - Some drug combinations may be more effective than others for schizophrenic patients
February 21, 2019 - Combination of common antibiotics can eliminate multi-drug resistant E. coli
February 21, 2019 - New computational tool searches for factors that cause specific diseases
February 21, 2019 - New method to assess effectiveness of psychotherapies for social anxiety disorder
February 21, 2019 - New technology measures hormones that influence reproductive health efficiently
February 21, 2019 - Bat influenza viruses could potentially attack the cells of humans and livestock
February 21, 2019 - Immunotherapeutic antibody therapy to kill cancer has now progressed to patient testing
February 21, 2019 - Johns Hopkins scientists find new compound that may prevent reperfusion injury
February 21, 2019 - Researchers develop new way to deliver treatment for cartilage regeneration
February 21, 2019 - Study sheds new light on left ventricular dysfunction in ischemic heart disease
February 21, 2019 - New technique could expedite cancer diagnosis, lead to better patient outcomes
February 21, 2019 - New map of infant brain may aid early diagnosis of autism
February 21, 2019 - Human consciousness depends on the brain’s ability to maintain dynamics of neural activity
February 21, 2019 - Harmony Biosciences Announces File Acceptance Of Its New Drug Application For Pitolisant
February 21, 2019 - Medications could fill treatment gap for adolescents with obesity
February 21, 2019 - New antibiotics are desperately needed: Machine learning could help | News Center
February 21, 2019 - Researchers develop new computer game for dementia carers
February 21, 2019 - University of Dundee partners with Takeda to develop new treatments for tau pathology
February 21, 2019 - Influenza vaccine may be less effective in elderly patients, finds study
February 21, 2019 - Researchers explain why T cells lose their protective ability in inflamed tissues
February 21, 2019 - New optimization method rapidly analyzes nanomedicines for cancer treatment
February 21, 2019 - Viruses in the intestinal tracts can lead to islet autoimmunity and Type 1 diabetes
February 21, 2019 - Link between dietary fatty acid intake and hypertension found to be influenced by diabetes status
February 21, 2019 - FDA Approves Esperoct (turoctocog alfa pegol, N8-GP) for Hemophilia A
February 21, 2019 - ‘Boy erased’—why conversion therapies and ex-gay ministries should be outlawed
February 21, 2019 - Titia de Lange to give annual McCormick Lecture on March 8 | News Center
February 21, 2019 - Study reveals how helper T cells support memory cells to function optimally
February 21, 2019 - Autistic children with co-occurring ADHD have greater adaptive behavior impairments
February 21, 2019 - Elevated levels of key cellular process implicated in intestinal inflammation and IBD
February 20, 2019 - Over Half of Hip Replacements Expected to Last 25 Years
February 20, 2019 - Microscopic eye movements affect how we see contrast
February 20, 2019 - Computer vs. patient: Fighting for residents’ attention | News Center
February 20, 2019 - New “Smart Drug” Shows Promise for Metastatic Triple-Negative Breast Cancer
February 20, 2019 - Researchers develop large-scale window material for high-efficiency PM2.5 capture
February 20, 2019 - Widespread confusion among consumers on food date labels lead to unnecessary discards
February 20, 2019 - Researchers unlock plant’s secret of producing specialized metabolites
February 20, 2019 - Newly released national framework identifies obstacles to improving EMS systems
February 20, 2019 - Exercise can shift human body clock depending on time when people work out
February 20, 2019 - Female adolescent blood donors more likely to have iron deficiency and related anemia
February 20, 2019 - Rubicon level linked to inhibition of autophagic process
February 20, 2019 - Researchers find potential therapeutic strategy to treat Alzheimer’s
February 20, 2019 - New forms of older anti-cancer agent appear to enhance immune response to fight melanoma
February 20, 2019 - Health Tip: Eat Less Saturated Fat
February 20, 2019 - Sleeping in contact lenses puts you at risk of dangerous infection
February 20, 2019 - “We should study that!”: How a nurse-scientist found her passion
February 20, 2019 - Cervical microbiome may influence HPV infection more than previously thought
February 20, 2019 - Sausage mislabeling in Canada is down, new study finds
February 20, 2019 - Study shows blood pressure benefits of morning exercise for older overweight/obese adults
February 20, 2019 - New screening method could catch organ rejection much earlier without a biopsy needle
February 20, 2019 - Study may have important implications for refining parenting during child’s adolescence
February 20, 2019 - Study sheds new light on how antibiotic resistance genes are transferred between bacteria
February 20, 2019 - Chronic Wasting Disease may soon spread to humans, warns CDC
February 20, 2019 - Scientists identify new genetic causes linked to abnormal pregnancies and miscarriages
February 20, 2019 - Using LyoSpeed technology to avoid residual solvent when drying HPLC fractions
February 20, 2019 - New AI can identify, predict development of different combinations of cancer symptoms
February 20, 2019 - Scientists join forces to identify a new approach to fight African sleeping sickness
February 20, 2019 - New screening tool more likely to identify sexual and labor exploitation of youth
February 20, 2019 - Newly licensed nurses work for long hours, also have a second paid job
February 20, 2019 - Physicists identify simple mechanism used by deadly bacteria to fend off antibiotics
February 20, 2019 - FDA Grants Priority Review to Genentech’s Personalized Medicine Entrectinib
February 20, 2019 - Exposure to chemicals before and after birth is associated with a decrease in lung function
February 20, 2019 - Neuroscientists reveal that simple brain region can guide complex feats of mental activity
February 20, 2019 - Study finds new link between food allergies and multiple sclerosis
February 20, 2019 - First gene therapy operation for macular degeneration is a success
Receptor structure could be key to developing new osteoporosis drugs

Receptor structure could be key to developing new osteoporosis drugs

image_pdfDownload PDFimage_print

Researchers at the University of Zurich have determined the three-dimensional structure of a receptor that controls the release of calcium from bones. The receptor is now one of the main candidates for developing new drugs to treat osteoporosis. Knowing the receptor’s blueprint will be instrumental for designing drugs that could even help to rebuild bones.

Osteoporosis affects about 400,000 people in Switzerland, mostly women after menopause. It is often described as a silent disease, because bone loss usually occurs little by little over the years and without any symptoms. The body gradually absorbs calcium from the bones, which become brittle. This process is controlled via what is called the parathyroid hormone (PTH) and a closely related peptide – a protein fragment. They bind to the PTH-1 receptor, thereby telling the body to either release calcium from the bone or to build new bone.

An extremely difficult undertaking

A team led by Andreas Plückthun, professor at the Department of Biochemistry of the University of Zurich (UZH), has now been able to determine the three-dimensional structure of the PTH-1 receptor. The atomic structure can now serve as the blueprint for the future development of drugs. Such receptor-binding compounds may slow down, and perhaps even reverse, osteoporosis to some degree. Determining the structure of this receptor was an extremely tough undertaking, as cells only produce a very small amount of it, and it is also very unstable. “The directed evolution and protein engineering methods we have developed over the last few years were absolutely instrumental in making this possible,” explains Andreas Plückthun.

Disadvantages of current treatment

One of the most effective current treatments for severe osteoporosis involves the use of substances that look like the natural hormone and its related peptide. “However, this treatment is extremely expensive. The substances have to be injected into the thigh or abdomen once a day, and the treatment also has significant side effects,” says Christoph Klenk, co-author of the study. The scientists are convinced that thanks to the new insights into the mechanisms of the PTH-1 receptor, new drugs can be developed that don’t have any of the previous disadvantages. “The receptor is like a lock, and the peptides are the keys that turn it,” describes Plückthun. “Having the atomic 3D blueprint on a computer screen gives us an unprecedented level of insight into how the lock actually works.”

Understanding a whole class of receptors

The PTH-1 receptor is a member of the family of G protein-coupled receptors. In particular, these include receptors that bind to other hormones, such as the ones involved in controlling diabetes. The work by the UZH scientists thus also sheds light on how the whole family of receptors works, as the PTH-1 receptor was examined at the highest level of detail for any of these receptors so far. This has enabled the scientists to describe similarities as well as differences to other class B receptors. “Having the blueprint of the lock doesn’t give us a key yet, but now it’s possible to build one,” says Andreas Plückthun.

Source:

https://www.media.uzh.ch/en/Press-Releases/2018/Osteoporosis.html

Posted in: Molecular & Structural Biology | Biochemistry

Tags: Biochemistry, Bone, Calcium, Diabetes, Drugs, Evolution, Hormone, Light, Menopause, Molecular Biology, Osteoporosis, Protein, Protein Engineering, Receptor

About author

Related Articles