Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-019-11931-1
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Funding
- DBT B-Life [DBT/PR12422/MED/31/287/2014]
- CSIR [CSIR/37/1606/13/EMR-II]
- Confederation of Indian Industry (CII)
- Evolva Biotech (Basel)
- Medical Research Council [U105184322]
- DOE Office of Biological and Environmental Research
- National Institute of Health project MINOS [R01GM105404]
- High-End Instrumentation Grant [S10OD018483]
- [BT/PR5081/INF/22/156/2012]
- MRC [MC_U105184326] Funding Source: UKRI
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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.
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