Jump to main content
Jump to site search

Issue 12, 2015
Previous Article Next Article

IspH–RPS1 and IspH–UbiA: “Rosetta stone” proteins

Author affiliations


The protein IspH, (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate (HMPPP) reductase, is an essential 4Fe–4S cluster-containing protein in the methylerythritol phosphate pathway for isoprenoid biosynthesis. Using a sequence similarity network we found that there are >400 IspH proteins that are about twice as large as most of the IspHs studied to date since their IspH domains are fused to either the ribosomal protein S1 (RPS1), or to a UbiA (4-hydroxybenzoate octaprenyltransferase)-like protein. Many of the IspH–RPS1 proteins are present in anaerobes found in the human gut and some, such as Clostridium botulinum, C. tetani and Fusobacterium nucleatum, are pathogens. The IspH–UbiAs are all found in sulfate-reducing anaerobes. The IspH domains in IspH–RPS1 are fused to 4 and in a few cases 6 tandem repeats in RPS1 that, in most organisms, bind to mRNA or form part of the bacterial ribosome. Mutants in which the four RPS1 domains were sequentially eliminated had similar IspH activity as wild-type protein, indicating they are not essential for IspH catalysis. Overall, the results are of interest since they represent the first isolation of a catalytically active IspH–RPS1, as well as the identification of IspH–UbiA hybrids, two “Rosetta stone” proteins that are likely to be functionally related—IspH producing the isoprenoids required for a UbiA-like prenyltransferase; the IspH–RPS1 hybrids, perhaps, being involved in the stringent response or as Fe/O2 sensors.

Graphical abstract: IspH–RPS1 and IspH–UbiA: “Rosetta stone” proteins

Back to tab navigation

Supplementary files

Publication details

The article was received on 18 Jul 2015, accepted on 04 Sep 2015 and first published on 07 Sep 2015

Article type: Edge Article
DOI: 10.1039/C5SC02600H
Citation: Chem. Sci., 2015,6, 6813-6822
  • Open access: Creative Commons BY license
  •   Request permissions

    IspH–RPS1 and IspH–UbiA: “Rosetta stone” proteins

    G. Rao, B. O'Dowd, J. Li, K. Wang and E. Oldfield, Chem. Sci., 2015, 6, 6813
    DOI: 10.1039/C5SC02600H

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author