Journal article
Molecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway
Nature communications, Vol.10(1), 4127
09/11/2019
DOI: 10.1038/s41467-019-11931-1
PMCID: PMC6739347
PMID: 31511507
Abstract
Substrate channeling is a mechanism for the internal transfer of hydrophobic, unstable or toxic intermediates from the active site of one enzyme to another. Such transfer has previously been described to be mediated by a hydrophobic tunnel, the use of electrostatic highways or pivoting and by conformational changes. The enzyme PaaZ is used by many bacteria to degrade environmental pollutants. PaaZ is a bifunctional enzyme that catalyzes the ring opening of oxepin-CoA and converts it to 3-oxo-5,6-dehydrosuberyl-CoA. Here we report the structures of PaaZ determined by electron cryomicroscopy with and without bound ligands. The structures reveal that three domain-swapped dimers of the enzyme form a trilobed structure. A combination of small-angle X-ray scattering (SAXS), computational studies, mutagenesis and microbial growth experiments suggests that the key intermediate is transferred from one active site to the other by a mechanism of electrostatic pivoting of the CoA moiety, mediated by a set of conserved positively charged residues.
Details
- Title: Subtitle
- Molecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway
- Creators
- Nitish Sathyanarayanan - Institute for Stem Cell Biology and Regenerative MedicineGiuseppe Cannone - MRC Laboratory of Molecular BiologyLokesh Gakhar - University of IowaNainesh Katagihallimath - Institute for Stem Cell Biology and Regenerative MedicineRamanathan Sowdhamini - National Centre for Biological SciencesSubramanian Ramaswamy - Inst Stem Cell Sci & Regenerat Med, GKVK Campus,Bellary Rd, Bangalore, Karnataka, IndiaKutti R. Vinothkumar - National Centre for Biological Sciences
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.10(1), 4127
- Publisher
- NATURE PORTFOLIO
- DOI
- 10.1038/s41467-019-11931-1
- PMID
- 31511507
- PMCID
- PMC6739347
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Number of pages
- 12
- Grant note
- U105184322 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) S10OD018483 / High-End Instrumentation Grant Evolva Biotech (Basel) R01GM105404 / National Institute of Health project MINOS Confederation of Indian Industry (CII) MC_U105184326 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) DBT/PR12422/MED/31/287/2014 / DBT B-Life DOE Office of Biological and Environmental Research; United States Department of Energy (DOE) CSIR/37/1606/13/EMR-II / CSIR; Council of Scientific & Industrial Research (CSIR) - India
- Language
- English
- Date published
- 09/11/2019
- Academic Unit
- Medicine Administration
- Record Identifier
- 9984632133702771
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