Volume 89 Issue 20 | p. 32 | Concentrates
Issue Date: May 16, 2011

Big Squeeze Clears Out Protein Garbarge

A mega cellular enzymatic machine undergoes a large conformational change to spit out its waste
Department: Science & Technology
News Channels: Analytical SCENE
Keywords: protease, antibiotics
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Pathogens discard proteins broken down by ClpP when the enzyme undergoes the conformational change shown to create equatorial pores.
Credit: Thomas Böttcher
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Pathogens discard proteins broken down by ClpP when the enzyme undergoes the conformational change shown to create equatorial pores.
Credit: Thomas Böttcher

X-ray crystallography has revealed how a huge cellular enzymatic machine called ClpP—used by pathogenic microbes to break down proteins—spits out its waste: A large conformational change squeezes the protease’s cylinder, thereby creating large equatorial pores from which the refuse diffuses away. Researchers are particularly interested in ClpP’s structure because pathogenic bacteria such as Staphylococcus aureus use the enzyme to destroy signals that block infection. Scientists see ClpP as a possible target for antimicrobial drugs, and knowing how it operates is helpful for those creating inhibitors. The first suggestion of ClpP’s compacting conformation came last year from the University of Toronto’s Walid A. Houry and colleagues, who predicted it would feature equatorial exit pores (Structure, DOI: 10.1016/j.str.2010.04.008). Biochemists led by Stephan A. Sieber at Germany’s Technical University of Munich and Patrick Cramer of Ludwig Maximilian University, also located in Munich, now show that the conformational change flattens ClpP by 10 Å and produces 14 equatorial side pores that are each about 6 Å in diameter (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201100666). The new ClpP structure could help drug designers create molecules that act as wrenches in pathogen garbage compactors.

 
Chemical & Engineering News
ISSN 0009-2347
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