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New sub-family of lysozyme-like proteins shows no catalytic activity: crystallographic and biochemical study of STM3605 protein from Salmonella Typhimurium

  • Published:
Journal of Structural and Functional Genomics

Abstract

Phage viruses that infect prokaryotes integrate their genome into the host chromosome; thus, microbial genomes typically contain genetic remnants of both recent and ancient phage infections. Often phage genes occur in clusters of atypical G+C content that reflect integration of the foreign DNA. However, some phage genes occur in isolation without other phage gene neighbors, probably resulting from horizontal gene transfer. In these cases, the phage gene product is unlikely to function as a component of a mature phage particle, and instead may have been co-opted by the host for its own benefit. The product of one such gene from Salmonella enterica serovar Typhimurium, STM3605, encodes a protein with modest sequence similarity to phage-like lysozyme (N-acetylmuramidase) but appears to lack essential catalytic residues that are strictly conserved in all lysozymes. Close homologs in other bacteria share this characteristic. The structure of the STM3605 protein was characterized by X-ray crystallography, and functional assays showed that it is a stable, folded protein whose structure closely resembles lysozyme. However, this protein is unlikely to hydrolyze peptidoglycan. Instead, STM3605 is presumed to have evolved an alternative function because it shows some lytic activity and partitions to micelles.

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Abbreviations

Rmsd:

Root-mean-square deviation

SAD:

Single-wavelength anomalous diffraction

SVM:

Support vector machine

PDB:

Protein Data Bank

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Acknowledgments

The authors would like to thank the members of the Midwest Center for Structural Biology and Structural Biology Center for their support. This research has been funded in part by a grant from the National Institutes of Health GM094585 (AJ), GM094623 (JNA), and by the US Department of Energy, Office of Biological and Environmental Research, under Contract DE-AC02-06CH11357. The authors wish to thank Gekleng Chhor for proofreading of this manuscript.

Author information

Authors and Affiliations

  1. The Midwest Center for Structural Genomics, Biosciences Division, Argonne National Laboratory, Argonne, IL, USA

    Karolina Michalska, Hui Li, Robert Jedrzejczak, Gyorgy Babnigg & Andrzej Joachimiak

  2. Structural Biology Center, Biosciences Division, Argonne National Laboratory, 9700 South Cass Avenue, Building 202, Argonne, IL, 60439, USA

    Karolina Michalska & Andrzej Joachimiak

  3. Center for Bioproducts and Bioenergy, Washington State University, Richland, WA, USA

    Roslyn N. Brown

  4. Department of Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA

    George S. Niemann & Fred Heffron

  5. Biological Sciences Division, Pacific Northwest National Laboratory, PO Box 999, MSIN: K8-98, Richland, WA, 99352, USA

    John R. Cort & Joshua N. Adkins

  6. Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA

    Andrzej Joachimiak

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  1. Karolina Michalska
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  2. Roslyn N. Brown
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  3. Hui Li
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Correspondence to Joshua N. Adkins or Andrzej Joachimiak.

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The submitted manuscript has been created by UChicago Argonne, LLC, Operator of Argonne National Laboratory (“Argonne”). Argonne, a US Department of Energy Office of Science laboratory, is operated under Contract No. DE-AC02-06CH11357. The US Government retains for itself, and others acting on its behalf, a paid-up nonexclusive, irrevocable worldwide license in said article to reproduce, prepare derivative works, distribute copies to the public, and perform publicly and display publicly, by or on behalf of the Government.

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Michalska, K., Brown, R.N., Li, H. et al. New sub-family of lysozyme-like proteins shows no catalytic activity: crystallographic and biochemical study of STM3605 protein from Salmonella Typhimurium. J Struct Funct Genomics 14, 1–10 (2013). https://doi.org/10.1007/s10969-013-9151-0

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  • DOI: https://doi.org/10.1007/s10969-013-9151-0

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