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Cofactor Tail Length Modulates Catalysis of Bacterial F420-Dependent Oxidoreductases

Overview of attention for article published in Frontiers in Microbiology, September 2017
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Title
Cofactor Tail Length Modulates Catalysis of Bacterial F420-Dependent Oxidoreductases
Published in
Frontiers in Microbiology, September 2017
DOI 10.3389/fmicb.2017.01902
Pubmed ID
Authors

Blair Ney, Carlo R. Carere, Richard Sparling, Thanavit Jirapanjawat, Matthew B. Stott, Colin J. Jackson, John G. Oakeshott, Andrew C. Warden, Chris Greening

Abstract

F420 is a microbial cofactor that mediates a wide range of physiologically important and industrially relevant redox reactions, including in methanogenesis and tetracycline biosynthesis. This deazaflavin comprises a redox-active isoalloxazine headgroup conjugated to a lactyloligoglutamyl tail. Here we studied the catalytic significance of the oligoglutamate chain, which differs in length between bacteria and archaea. We purified short-chain F420 (two glutamates) from a methanogen isolate and long-chain F420 (five to eight glutamates) from a recombinant mycobacterium, confirming their different chain lengths by HPLC and LC/MS analysis. F420 purified from both sources was catalytically compatible with purified enzymes from the three major bacterial families of F420-dependent oxidoreductases. However, long-chain F420 bound to these enzymes with a six- to ten-fold higher affinity than short-chain F420. The cofactor side chain also significantly modulated the kinetics of the enzymes, with long-chain F420 increasing the substrate affinity (lower Km) but reducing the turnover rate (lower kcat) of the enzymes. Molecular dynamics simulations and comparative structural analysis suggest that the oligoglutamate chain of F420 makes dynamic electrostatic interactions with conserved surface residues of the oxidoreductases while the headgroup binds the catalytic site. In conjunction with the kinetic data, this suggests that electrostatic interactions made by the oligoglutamate tail result in higher-affinity, lower-turnover catalysis. Physiologically, we propose that bacteria have selected for long-chain F420 to better control cellular redox reactions despite tradeoffs in catalytic rate. Conversely, this suggests that industrial use of shorter-length F420 will greatly increase the rates of bioremediation and biocatalysis processes relying on purified F420-dependent oxidoreductases.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 24%
Researcher 5 17%
Student > Bachelor 3 10%
Student > Master 2 7%
Student > Postgraduate 2 7%
Other 2 7%
Unknown 8 28%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 28%
Biochemistry, Genetics and Molecular Biology 7 24%
Chemistry 2 7%
Environmental Science 1 3%
Medicine and Dentistry 1 3%
Other 1 3%
Unknown 9 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 October 2017.
All research outputs
#15,821,622
of 23,498,099 outputs
Outputs from Frontiers in Microbiology
#15,792
of 25,939 outputs
Outputs of similar age
#202,320
of 321,739 outputs
Outputs of similar age from Frontiers in Microbiology
#337
of 511 outputs
Altmetric has tracked 23,498,099 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 25,939 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one is in the 30th percentile – i.e., 30% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 321,739 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 511 others from the same source and published within six weeks on either side of this one. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.