Skip to main content
padlock icon - secure page this page is secure

Open Access Characterisation of the Z-pocket for the treatment of alpha-1-antitrypsin deficiency – MRC

Download Article:
(PDF 430.6 kb)
Alpha-1-antitrypsin (a1AT) deficiency is a relatively common genetic disorder resulting in lung and liver diseases, such as emphysema, cirrhosis and cancer. There is currently no cure or treatment. The most common cause is the 'Z' mutation which leads to the accumulation of misfolded a1AT 'polymers' in liver cells. As part of a previous MRC grant, we discovered a surprising mechanism of Z-a1AT polymerization and the structural feature that causes Z-a1AT to misfold. The goal of the current research is to study the feature, that we named the 'Z-pocket', in more detail. Compounds that bind to the Z-pocket could rescue the folding of Z-a1AT and effectively cure the disease. We will use X-ray crystallography and nuclear magnetic resonance to determine the properties of the Z-pocket and to see if previously identified compounds rescue folding by filling the pocket. Successful completion of this project will set the stage for the discovery of new drugs for the treatment of a1AT-deficiency.
No References for this article.
No Supplementary Data.
No Article Media
No Metrics


Document Type: Research Article

Publication date: May 1, 2017

More about this publication?
  • Impact is a series of high-quality, open access and free to access science reports designed to enable the dissemination of research impact to key stakeholders. Communicating the impact and relevance of research projects across a large number of subjects in a content format that is easily accessible by an academic and stakeholder audience. The publication features content from the world's leading research councils, policy groups, universities and research projects. Impact is published under a CC-BY Creative Commons licence.

  • Subscribe to this Title
  • Terms & Conditions
  • Disseminating research in Impact
  • Information about Impact
  • Ingenta Connect is not responsible for the content or availability of external websites
  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more