4urr

Tailspike protein of Sf6 bacteriophage bound to Shigella flexneri O- antigen octasaccharide fragmentTailspike protein of Sf6 bacteriophage bound to Shigella flexneri O- antigen octasaccharide fragment

Structural highlights

4urr is a 6 chain structure with sequence from Shigella virus Sf6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.95Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FIBER_BPSFV Non-covalently bound to the neck of the phage capsid and mediating attachment of the viral particle to host cell-surface polysaccharide. It displays endorhamnosidase enzymatic activity, hydrolyzing the alpha-1,3-O-glycosidic linkage between rhamnose and galactose of the O-antigen polysaccharide.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Understanding interactions of bacterial surface polysaccharides with receptor protein scaffolds is important for the development of antibiotic therapies. The corresponding protein recognition domains frequently form low-affinity complexes with polysaccharides that are difficult to address with experimental techniques due to the conformational flexibility of the polysaccharide. In this work, we studied the tailspike protein (TSP) of the bacteriophage Sf6. Sf6TSP binds and hydrolyzes the high-rhamnose, serotype Y O-antigen polysaccharide of the Gram-negative bacterium Shigella flexneri (S. flexneri) as a first step of bacteriophage infection. Spectroscopic analyses and enzymatic cleavage assays confirmed that Sf6TSP binds long stretches of this polysaccharide. Crystal structure analysis and saturation transfer difference (STD) NMR spectroscopy using an enhanced method to interpret the data permitted the detailed description of affinity contributions and flexibility in an Sf6TSP-octasaccharide complex. Dodecasaccharide fragments corresponding to three repeating units of the O-antigen in complex with Sf6TSP were studied computationally by molecular dynamics simulations. They showed that distortion away from the low-energy solution conformation found in the octasaccharide complex is necessary for ligand binding. This is in agreement with a weak-affinity functional polysaccharide-protein contact that facilitates correct placement and thus hydrolysis of the polysaccharide close to the catalytic residues. Our simulations stress that the flexibility of glycan epitopes together with a small number of specific protein contacts provide the driving force for Sf6TSP-polysaccharide complex formation in an overall weak-affinity interaction system.

Bacteriophage Tailspikes and Bacterial O-Antigens as a Model System to Study Weak-Affinity Protein-Polysaccharide Interactions.,Kang Y, Gohlke U, Engstrom O, Hamark C, Scheidt T, Kunstmann S, Heinemann U, Widmalm G, Santer M, Barbirz S J Am Chem Soc. 2016 Jul 27;138(29):9109-18. doi: 10.1021/jacs.6b00240. Epub 2016 , Apr 25. PMID:27045683^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Muller JJ, Barbirz S, Heinle K, Freiberg A, Seckler R, Heinemann U. An intersubunit active site between supercoiled parallel beta helices in the trimeric tailspike endorhamnosidase of Shigella flexneri Phage Sf6. Structure. 2008 May;16(5):766-75. PMID:18462681 doi:10.1016/j.str.2008.01.019
↑ Freiberg A, Morona R, Van den Bosch L, Jung C, Behlke J, Carlin N, Seckler R, Baxa U. The tailspike protein of Shigella phage Sf6. A structural homolog of Salmonella phage P22 tailspike protein without sequence similarity in the beta-helix domain. J Biol Chem. 2003 Jan 17;278(3):1542-8. PMID:12424253 doi:10.1074/jbc.M205294200
↑ Iwashita S, Kanegasaki S. Enzymic and molecular properties of base-plate parts of bacteriophage P22. Eur J Biochem. 1976 May 17;65(1):87-94. PMID:6284 doi:10.1111/j.1432-1033.1976.tb10392.x
↑ Kang Y, Gohlke U, Engstrom O, Hamark C, Scheidt T, Kunstmann S, Heinemann U, Widmalm G, Santer M, Barbirz S. Bacteriophage Tailspikes and Bacterial O-Antigens as a Model System to Study Weak-Affinity Protein-Polysaccharide Interactions. J Am Chem Soc. 2016 Jul 27;138(29):9109-18. doi: 10.1021/jacs.6b00240. Epub 2016 , Apr 25. PMID:27045683 doi:http://dx.doi.org/10.1021/jacs.6b00240

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OCA

[1] Muller JJ, Barbirz S, Heinle K, Freiberg A, Seckler R, Heinemann U. An intersubunit active site between supercoiled parallel beta helices in the trimeric tailspike endorhamnosidase of Shigella flexneri Phage Sf6. Structure. 2008 May;16(5):766-75. PMID:18462681 doi:10.1016/j.str.2008.01.019

[2] Freiberg A, Morona R, Van den Bosch L, Jung C, Behlke J, Carlin N, Seckler R, Baxa U. The tailspike protein of Shigella phage Sf6. A structural homolog of Salmonella phage P22 tailspike protein without sequence similarity in the beta-helix domain. J Biol Chem. 2003 Jan 17;278(3):1542-8. PMID:12424253 doi:10.1074/jbc.M205294200

[3] Iwashita S, Kanegasaki S. Enzymic and molecular properties of base-plate parts of bacteriophage P22. Eur J Biochem. 1976 May 17;65(1):87-94. PMID:6284 doi:10.1111/j.1432-1033.1976.tb10392.x

[4] Kang Y, Gohlke U, Engstrom O, Hamark C, Scheidt T, Kunstmann S, Heinemann U, Widmalm G, Santer M, Barbirz S. Bacteriophage Tailspikes and Bacterial O-Antigens as a Model System to Study Weak-Affinity Protein-Polysaccharide Interactions. J Am Chem Soc. 2016 Jul 27;138(29):9109-18. doi: 10.1021/jacs.6b00240. Epub 2016 , Apr 25. PMID:27045683 doi:http://dx.doi.org/10.1021/jacs.6b00240

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