Crystal structure of the Salmonella enterica serovar typhimurium virulence factor SrfJ, a glycoside hydrolase family enzyme.
To cause infection, Salmonella enterica serovar Typhimurium uses type III secretion systems, which are encoded on two Salmonella pathogenicity islands, SPI-1 and SPI-2, the latter of which is thought to play a crucial role in bacterial proliferation in Salmonella-containing vacuoles (SCVs) after invading cells. S. Typhimurium SrfJ, located outside SPI-2, is also known to be involved in Salmonella pathogenicity and has high amino acid sequence homology with human lysosomal glucosylceramidase (GlcCerase). We present the first crystal structure of SrfJ at a resolution of 1.8 A. The overall fold of SrfJ shares high structure similarities with that of human GlcCerase, comprising two distinctive domains: a (beta/alpha)(8)-barrel catalytic domain and a beta-sandwich domain. As in human GlcCerase, the pocket-shaped active site of SrfJ is located on the C-terminal side of the barrel, and two conserved glutamic acid residues are used for the enzyme catalysis. Moreover, a glycerol-bound form of SrfJ reveals that the glucose ring moiety of the substrate might similarly bind to the enzyme as to human GlcCerase, suggesting that SrfJ might function as a glycoside hydrolase. Although some structural differences are observed between SrfJ and human GlcCerase in the substrate entrance of the active site, we speculate that, based on the high structural similarities to human GlcCerase in the overall fold and the active-site environment, SrfJ might have a GlcCerase activity and use the activity to enhance Salmonella virulence by modifying SCV membrane lipids.
Kim
Yeon-Gil
YG
Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, South Korea.
Kim
Jin-Hong
JH
Kim
Kyung-Jin
KJ
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D003001:Cloning, Molecular; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006026:Glycoside Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D016415:Sequence Alignment; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D037521:Virulence Factors; D006026:Glycoside Hydrolases