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Title: Structure and proposed mechanism of α-glycerophosphate oxidase from Mycoplasma pneumoniae

Journal Article · · Federation of European Biochemical Societies (FEBS) Journal
DOI:https://doi.org/10.1111/febs.13233· OSTI ID:1240120
 [1];  [1];  [2];  [3];  [4];  [5];  [1]
  1. Oregon State Univ., Corvallis, OR (United States)
  2. Center for Structural Biology, Wake Forest School of Medicine, Winston-Salem NC USA
  3. Burapha Univ., Chonburi (Thailand)
  4. Mahidol Univ., Bangkok (Thailand)
  5. Wake Forest School of Medicine, Winston-Salem, NC (United States)
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In this study, the formation of hydrogen peroxide (H₂O₂) by the FAD-dependent α-glycerophosphate oxidase (GlpO), is important for the pathogenesis of Streptococcus pneumoniae and Mycoplasma pneumoniae. The structurally known GlpO from Streptococcus sp. (SspGlpO) is similar to the pneumococcal protein (SpGlpO) and provides a guide for drug design against that target. However, M. pneumoniae GlpO (MpGlpO), having <20% sequence identity with structurally known GlpOs, appears to represent a second type of GlpO we designate as Type II GlpOs. Here, the recombinant His-tagged MpGlpO structure is described at ~2.5 Å resolution, solved by molecular replacement using as a search model the Bordetella pertussis protein 3253 (Bp3253) a protein of unknown function solved by structural genomics efforts. Recombinant MpGlpO is an active oxidase with a turnover number of ~580 min⁻¹ while Bp3253 showed no GlpO activity. No substantial differences exist between the oxidized and dithionite-reduced MpGlpO structures. Although, no liganded structures were determined, a comparison with the tartrate-bound Bp3253 structure and consideration of residue conservation patterns guided the construction of a model for α-glycerophosphate (Glp) recognition and turnover by MpGlpO. The predicted binding mode also appears relevant for the type I GlpOs (such as SspGlpO) despite differences in substrate recognition residues, and it implicates a histidine conserved in type I and II Glp oxidases and dehydrogenases as the catalytic acid/base. This work provides a solid foundation for guiding further studies of the mitochondrial Glp dehydrogenases as well as for continued studies of M. pneumoniae and S. pneumoniae glycerol metabolism and the development of novel therapeutics targeting MpGlpO and SpGlpO.

Research Organization:
Oregon State Univ., Corvallis, OR (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-98CH10886
OSTI ID:
1240120
Journal Information:
Federation of European Biochemical Societies (FEBS) Journal, Vol. 282, Issue 16; ISSN 1742-464X
Publisher:
Federation of European Biochemical SocietiesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 14 works
Citation information provided by
Web of Science

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Cited By (4)

Potential Molecular Targets for Narrow-Spectrum Agents to Combat Mycoplasma pneumoniae Infection and Disease journal February 2016
Insights into the pathogenesis of Mycoplasma pneumoniae journal September 2016
Hydrogen sulfide is a novel potential virulence factor of M ycoplasma pneumoniae : characterization of the unusual cysteine desulfurase/desulfhydrase HapE: Hydrogen sulfide production in Mycoplasma journal February 2016
Glycerol metabolism and its implication in virulence in Mycoplasma journal July 2017

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