Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

3D Structure of Key Protein in Fight Against Homocystinuria Unveiled

Published: Wednesday, December 18, 2013
Last Updated: Wednesday, December 18, 2013
Bookmark and Share
The disease is caused by an increased plasma concentration of homocysteine, which is a toxic metabolite.

Homocystinuria is a disease caused by the deficiency or anomalous function of a protein, with serious consequences such as skeletal deformities, vascular thrombosis and even mental retardation. It is a disease that is classed as “rare” and its incidence varies between 1 in 50,000 and 1 in 200,000 individuals and its mortality rate is 18% by age 30, although some studies reveal higher numbers. 

The key to fight against this disease lies in the CBS protein, which is essential in the regulation of transsulfuration, the process that our body carries out to recycle homocysteine into beneficial amino acids, such as methionine or cysteine.

There has currently been a breakthrough in the fight against homocystinuria thanks to research carried out at CIC bioGUNE, led by Luis-Alfonso Martínez de la Cruz, head of a research team at the X-ray Crystallography Unit. The research has managed to solve the 3D structure of the key enzyme – CBS. The research, in which Martínez Cruz has worked alongside researchers June Ereño and Iker Oyenarte, from CIC bioGUNE, and has collaborated with the University of Colorado, was recently published in the prestigious journal Proceedings of the National Academy of Sciences of the United States of America.

Under normal conditions, homocysteine concentration levels remain within a range finely regulated by the action of several enzymes (proteins that catalyse chemical reactions), which maintain the balance between its production and degradation and prevent it from becoming toxic. The main regulatory enzyme is CBS (cystathionine beta-synthase).

The deficiency in the CBS enzyme’s activity is directly connected with mutations in the gene that codes it and an incorrect 3D structure of the protein, causing increased plasma concentration of homocysteine.

This condition is known as hyperhomocysteinaemia or homocystinuria and it is an important risk factor in the development of syndromes causing mental retardation, childhood developmental problems, visual impairment and severe episodes of arterial and venous thrombosis, which cause stroke and heart attacks before 30 years of age.

That is why the research carried out at the laboratory led by Luis-Alfonso Martínez Cruz at CIC bioGUNE is so important, as it provides a breakthrough in the fight against this disease thanks to the discovery of the 3D structure of the CBS protein, an atomic resolution 3D mould, which will help to design drugs that modulate its biological activity. The importance of this protein in the human metabolism makes it an attractive therapeutic target, so it may lead to the future development of drugs that regulate its activity in cases in which its correct function is interrupted by the presence of mutations.

In order to develop these drugs, it is essential to know the 3D structure of this protein, so that the drugs may affect its regulation and way of acting. The fact that this 3D structure has been solved is relevant in two ways: On one hand, it provides a 3D map of the exact location of the mutations described in patients up until now, and this enables the explanation of how these mutations affect the correct function of the enzyme.

On the other hand, it will enable the development of drugs that restore the correct functionality of the enzyme in patients in which it has been rendered useless by a mutation.

The discovery of the 3D structure of the human CBS has been solved using a structural biology technique known as X-ray diffraction crystallography, which involves interpreting the diffraction pattern that is generated when an X-ray beam falls on a protein crystal whose structure is being determined. CIC bioGUNE owns cutting-edge X-ray diffraction facilities.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Researchers Reveal Evolution of Prehistoric Protein in the Human Body
Research carried out by the Basque Centre for Biosciences, CIC bioGUNE, and the universities of Yale, Harvard and Oxford, shows that the enzyme that converts DNA into RNA has been conserved in the human body since appearing in ancestral unicellular organisms 2 billion years ago.
Monday, May 18, 2009
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
Kitchen Utensils Can Spread Bacteria Between Foods
In a recent study researchers found that produce that contained bacteria would contaminate other produce items through the continued use of knives or graters—the bacteria would latch on to the utensils commonly found in consumers' homes and spread to the next item.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Safer, Faster Way To Remove Pollutants From Water
Using nanoparticles filled with enzymes proves more effective than current methods.
Drug May Prevent Life-Threatening Muscle Loss in Advanced Cancers
New data describes how an experimental drug can stop life-threatening muscle wasting (cachexia) associated with advanced cancers and restore muscle health.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
Novel Tumor Treatment
In the first published results from a $386,000 National Cancer Institute grant awarded earlier this year, a paper by Scott Verbridge and Rafael Davalos has been published.
Speeding Up the Process of Making Vaccines
System uses a freeze-dry concept to develop "just-add-water" solution.
Chemical Design Made Easier
Rice University scientists prepare elusive organocatalysts for drug and fine chemical synthesis.
New Analysis Technique for Chiral Activity in Molecules
Professor Hyunwoo Kim of the Chemistry Department and his research team have developed a technique that can easily analyze the optical activity of charged compounds by using nuclear magnetic resonance (NMR) spectroscopy.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos