Characterization of the structure and catalytic activity of Legionella pneumophila VipF

Young, Byron H.; Caldwell, Tracy A.; McKenzie, Aidan M.; Kokhan, Oleksandr; Berndsen, Christopher E.

doi:10.1002/prot.25087

Characterization of the structure and catalytic activity of Legionella pneumophila VipF

Journal Article · Tue Jul 05 00:00:00 EDT 2016 · Proteins

DOI:https://doi.org/10.1002/prot.25087· OSTI ID:1401692

Young, Byron H. ^[1]; Caldwell, Tracy A. ^[1]; McKenzie, Aidan M. ^[1]; Kokhan, Oleksandr ^[1]; ^[1]

Department of Chemistry and Biochemistry James Madison University Harrisonburg Virginia 22807

ABSTRACT

The pathogenic bacteria Legionella pneumophila is known to cause Legionnaires' Disease, a severe pneumonia that can be fatal to immunocompromised individuals and the elderly. Shohdy et al . identified the L. pneumophila vacuole sorting inhibitory protein VipF as a putative N ‐acetyltransferase based on sequence homology. We have characterized the basic structural and functional properties of VipF to confirm this original functional assignment. Sequence conservation analysis indicates two putative CoA‐binding regions within VipF. Homology modeling and small angle X‐ray scattering suggest a monomeric, dual‐domain structure joined by a flexible linker. Each domain contains the characteristic beta‐splay motif found in many acetyltransferases, suggesting that VipF may contain two active sites. Docking experiments suggest reasonable acetyl‐CoA binding locations within each beta‐splay motif. Broad substrate screening indicated that VipF is capable of acetylating chloramphenicol and both domains are catalytically active. Given that chloramphenicol is not known to be N ‐acetylated, this is a surprising finding suggesting that VipF is capable of O ‐acetyltransferase activity. Proteins 2016; 84:1422–1430. © 2016 Wiley Periodicals, Inc.

View Accepted Manuscript (Publisher)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1401692

Alternate ID(s):: OSTI ID: 1327060

Journal Information:: Proteins, Journal Name: Proteins Journal Issue: 10 Vol. 84; ISSN 0887-3585

Publisher:: Wiley Blackwell (John Wiley & Sons)Copyright Statement

Country of Publication:: United States

Language:: English

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