@article {1843,
	title = {Molecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway.},
	journal = {Nat Commun},
	volume = {10},
	year = {2019},
	month = {2019 Sep 11},
	pages = {4127},
	abstract = {<p>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.</p>
},
	issn = {2041-1723},
	doi = {10.1038/s41467-019-11931-1},
	author = {Sathyanarayanan, Nitish and Cannone, Giuseppe and Gakhar, Lokesh and Katagihallimath, Nainesh and Sowdhamini, Ramanathan and Ramaswamy, Subramanian and Vinothkumar, Kutti R}
}
