Journal article
Manipulating the lewis antigen specificity of the cholesterol-dependent cytolysin lectinolysin
SL Lawrence, SC Feil, JK Holien, MJ Kuiper, L Doughty, O Dolezal, TD Mulhern, RK Tweten, MW Parker
Frontiers in Immunology | FRONTIERS MEDIA SA | Published : 2012
Open access
Abstract
The cholesterol-dependent cytolysins (CDCs) attack cells by punching large holes in their membranes. LectinolysinfromStreptococcusmitis isuniqueamongCDCs due to the presence of an N-terminal lectin domain that enhances the pore-forming activity of the toxin. We recently determined the crystal structures of the lectin domain in complex with various glycans.These structures revealed the molecular basis for the Lewis antigen specificity of the toxin. Based on this information we have used in silico molecular modeling to design a mutant toxin, which we predicted would increase its specificity for Lewis y, an antigen found on the surface of cancer cells. Surprisingly, we found by surface plasmon ..
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Awarded by Victorian Life Sciences Computation Initiative (VLSCI)
Awarded by National Institutes of Health
Funding Acknowledgements
This research was partly undertaken on the MX2 beamline at the Australian Synchrotron, Victoria, Australia. We thank Dr. Torn Caradoc-Davies and the other beamline staff for their assistance, We also thank Dr. Jerome Widens for assistance with X-ray crystallographic data collection, This work was partly carried out in the Australian Cancer Research Foundation Rational Drug Discovery Centre and funding was received from the Victorian Government Operational Infrastructure Support Scheme to St. Vincent's Institute. This research was supported by a Victorian Life Sciences Computation Initiative (VLSCI) grant number VR0021 on its Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government, Australia, Rodney K. Tweten received support from Grant AI037657 from the National Institutes of Health. Susanne C. Feil was supported by a NHMRC Industry Fellowship. Michael W. Parker is an NHMRC Research Fellow.