1. Subversion of host cells causing Legionnaires' diseaseJoel D. Brock, Cornell University, DMR 0936384 Intellectual Merit: Legionella pneumophilais a bacterium which can be found in the stagnant water of poorly-maintained air conditioning systems and similar environments, and is linked to sporadic outbreaks of the human affliction known as Legionnaires' disease. When L. pneumophilacells are inhaled into the lungs, they are swallowed by immune cells known as macrophages. Recent evidence indicates that the manipulation performed by L. pneumophilainvolves skewing the host's balance of phosphoinositides. How this feat was accomplished remained an outstanding mystery. The Mao and Luo groups crystallized the SidF protein and solved its molecular structure through X-ray crystallography with data collected at CHESS. They solved the structure of the enzyme alone and the enzyme with a phosphoinositide bound in the active site, revealing considerable details of the binding mechanism. Recognition by SidF of the substrate molecule shown as a stick-figure inside a yellow envelope at the catalytic site. The binding of the substrate induces a large conformational change of a loop containing the His233 residue. FoSheng Hsu, Wenhan Zhu, Lucy Brennan, Lili Tao, Zhao-Qing Luo, and Yuxin Mao; "Structural Basis for Substrate Recognition by a Unique Legionella Phosphoinositide Phosphatase", PNAS vol.109, no. 34, pp. 13567-13572; doi: 10.1073/pnas.1207903109 (August 21, 2012) CHESS DMR-0936384 October 2012