The basis for non-canonical ROK family function in the N-acetylmannosamine kinase from the pathogen Staphylococcus aureus

D Coombes; JS Davies; MC Newton-Vesty; CR Horne; TG Setty; R Subramanian; JWB Moir; R Friemann; S Panjikar; MDW Griffin; RA North; RCJ Dobson

Journal article

The basis for non-canonical ROK family function in the N-acetylmannosamine kinase from the pathogen Staphylococcus aureus

D Coombes, JS Davies, MC Newton-Vesty, CR Horne, TG Setty, R Subramanian, JWB Moir, R Friemann, S Panjikar, MDW Griffin, RA North, RCJ Dobson

Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2020

DOI: 10.1074/jbc.RA119.010526

Abstract

In environments where glucose is limited, some pathogenic bacteria metabolize host-derived sialic acid as a nutrient source. N-Acetylmannosamine kinase (NanK) is the second enzyme of the bacterial sialic acid import and degradation pathway and adds phosphate to N-acetylmannosamine using ATP to prime the molecule for future pathway reactions. Sequence alignments reveal that Gram-positive NanK enzymes belong to the Repressor, ORF, Kinase (ROK) family, but many lack the canonical Zn-binding motif expected for this function, and the sugar-binding EXGH motif is altered to EXGY. As a result, it is unclear how they perform this important reaction. Here, we study the Staphylococcus aureus NanK (SaNa..

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University of Melbourne Researchers

Chris Horne Author

Michael Griffin Author

Renwick Dobson Author

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Grants

Awarded by University of Canterbury

Funding Acknowledgements

This work was supported by in part by New Zealand Royal Society Marsden Fund contract UOC1506, Ministry of Business, Innovation and Employment Smart Ideas Grant UOCX1706, and the Biomolecular Interactions Centre (University of Canterbury) (to R. C. J. D.), Australian Research Council Future Fellowship project FT140100544 (to M. D. W. G.), University of Canterbury Doctoral Scholarships (to D. C. and R. A. N.), New Zealand Royal Society Marsden Fund contract UOC1506 (to R. A. N.), DBT-Indo Swedish Grant BT/IN/SWEDEN/06/SR/2017-18 (to R. S. and T. G. S.), a Senior Research fellowship from the Council of Scientific and Industrial Research (CSIR) (to T. G. S.), Swedish Governmental Agency for Innovation Systems (VINNOVA) Grant 2017-00180 (to R. F.) and the Centre for Antibiotic Resistance Research (CARe) at University of Gothenburg (to R. F.), and an Erskine distinguished Visiting Fellowship (to J. W. B. M.). The authors declare that they have no conflicts of interest with the contents of this article.