In 1976, 152 people contracted a severe respiratory disease while attending an American Legion convention in Philadelphia; 22 of the patients died. The culprit of this disease - called the Legionnaires' disease because of the outbreak at the convention - is a rod-shaped bacterium called Legionella pneumophila. The bacteria live in warm stagnant water sources, such as in air conditioning cooling towers, shower heads or humidifiers, and are transmitted to humans through inhaling the water droplets generated by these devices. Because ~70% of the cases of the Legionnaires' disease are in epidemic form, both prevention and development of treatment against the disease are important tasks.
At the early stage of L. pneumophila infection, the bacteria multiply inside human lung cells. This capability is enhanced by a bacterial protein called macrophage infectivity potentiator protein (Mip). Mip has an enzyme activity that speeds up the protein folding reaction, although it is not yet known if this activity is involved in L. pneumophila infection. To begin to understand the role of Mip in L. pneumophila infection, Hilgenfeld and coworkers at the Institute of Molecular Biotechnology, Germany, have determined the crystal structure of Mip (Nature Structural Biology, Vol. 8, No. 9, pages 779-783).
The molecular architecture of Mip is a V-shaped dimer. At the diverging ends of the V are two domains that can bind FK506, a compound that inhibits the enzyme activity of Mip. By also determining the structure of Mip in complex with FK506, the authors have provided details of how this compound binds to the protein. Because FK506 is an immunsuppressant, it is not an appropriate drug for treating L. pneumophila infection. Nonetheless, these results represent a starting point from which rational searches for host cell protein(s) that interact with Mip, as well as drugs that specifically target Mip, can be initiated.
Professor Rolf Hilgenfeld
Institute of Molecular Biotechnology
Structural Biology & Crystallography
P.O. Box 100813
Telephone: 49 3641 65 6061
Fax: 49 3641 65 6062
(C) Nature Structural Biology press release.
Message posted by: Trevor M. D'Souza
Variants Associated with Pediatric Allergic Disorder
Mutations in PHF6 Found in T-Cell Leukemia
Genetic Risk Variant for Urinary Bladder Cancer
Antibody Has Therapeutic Effect on Mice with ALS
Regulating P53 Activity in Cancer Cells
Anti-RNA Therapy Counters Breast Cancer Spread
Mitochondrial DNA Diversity
The Power of RNA Sequencing
‘Pro-Ageing' Therapy for Cancer?
Niche Genetics Influence Leukaemia
Molecular Biology: Clinical Promise for RNA Interference
Chemoprevention Cocktail for Colon Cancer
more news ...