4FYG

Structural basis for substrate recognition by a novel Legionella phosphoinositide phosphatase

Summary for 4FYG

• Entry DOI: 10.2210/pdb4fyg/pdb
• Related: 4FYE 4FYF
• Descriptor: SidF, inhibitor of growth family, member 3, (2R)-3-{[(S)-hydroxy{[(1S,2R,3R,4S,5S,6S)-2,3,6-trihydroxy-4,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl dibutanoate (3 entities in total)
• Functional Keywords: mixed alpha-beta, phosphoinositide phosphatase, phosphoinositides, membrane, hydrolase
• Biological source: Legionella pneumophila subsp. pneumophila
• Total number of polymer chains: 1
• Total formula weight: 86825.71

Authors

Hsu, F.S.,Zhu, W.,Brennan, L.,Tao, L.,Luo, Z.Q.,Mao, Y. (deposition date: 2012-07-04, release date: 2012-08-22, Last modification date: 2023-09-13)

Primary citation

Hsu, F.,Zhu, W.,Brennan, L.,Tao, L.,Luo, Z.Q.,Mao, Y.
Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase.
Proc.Natl.Acad.Sci.USA, 109:13567-13572, 2012

PubMed Abstract: Legionella pneumophila is an opportunistic intracellular pathogen that causes sporadic and epidemic cases of Legionnaires' disease. Emerging data suggest that Legionella infection involves the subversion of host phosphoinositide (PI) metabolism. However, how this bacterium actively manipulates PI lipids to benefit its infection is still an enigma. Here, we report that the L. pneumophila virulence factor SidF is a phosphatidylinositol polyphosphate 3-phosphatase that specifically hydrolyzes the D3 phosphate of PI(3,4)P(2) and PI(3,4,5)P(3). This activity is necessary for anchoring of PI(4)P-binding effectors to bacterial phagosomes. Crystal structures of SidF and its complex with its substrate PI(3,4)P(2) reveal striking conformational rearrangement of residues at the catalytic site to form a cationic pocket that specifically accommodates the D4 phosphate group of the substrate. Thus, our findings unveil a unique Legionella PI phosphatase essential for the establishment of lipid identity of bacterial phagosomes.

PubMed: 22872863
DOI: 10.1073/pnas.1207903109

Experimental method

X-RAY DIFFRACTION (2.822 Å)