4EXM: The Crystal Structure Of An Engineered Phage Lysin Containing The Binding Domain Of Pesticin And The Killing Domain Of T4-lysozyme

Citation:
Abstract
Bacterial pathogens are becoming increasingly resistant to antibiotics. As an alternative therapeutic strategy, phage therapy reagents containing purified viral lysins have been developed against gram-positive organisms but not against gram-negative organisms due to the inability of these types of drugs to cross the bacterial outer membrane. We solved the crystal structures of a Yersinia pestis outer membrane transporter called FyuA and a bacterial toxin called pesticin that targets this transporter. FyuA is a beta-barrel membrane protein belonging to the family of TonB dependent transporters, whereas pesticin is a soluble protein with two domains, one that binds to FyuA and another that is structurally similar to phage T4 lysozyme. The structure of pesticin allowed us to design a phage therapy reagent comprised of the FyuA binding domain of pesticin fused to the N-terminus of T4 lysozyme. This hybrid toxin kills specific Yersinia and pathogenic E. coli strains and, importantly, can evade the pesticin immunity protein (Pim) giving it a distinct advantage over pesticin. Furthermore, because FyuA is required for virulence and is more common in pathogenic bacteria, the hybrid toxin also has the advantage of targeting primarily disease-causing bacteria rather than indiscriminately eliminating natural gut flora.
PDB ID: 4EXMDownload
MMDB ID: 100744
PDB Deposition Date: 2012/4/30
Updated in MMDB: 2017/07
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Similar Structures:
Biological Unit for 4EXM: dimeric; determined by author and by software (PISA)
Molecular Components in 4EXM
Label Count Molecule
Proteins (2 molecules)
2
Pesticin, Lysozyme Chimera(Gene symbol: e)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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