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Title | Molecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway. |
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Journal, issue, pages | Nat Commun, Vol. 10, Issue 1, Page 4127, Year 2019 |
Publish date | Sep 11, 2019 |
![]() | Nitish Sathyanarayanan / Giuseppe Cannone / Lokesh Gakhar / Nainesh Katagihallimath / Ramanathan Sowdhamini / Subramanian Ramaswamy / Kutti R Vinothkumar / ![]() ![]() ![]() |
PubMed 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 ...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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Methods | EM (single particle) |
Resolution | 2.9 - 3.3 Å |
Structure data | EMDB-9873, PDB-6jql: |
Chemicals | ![]() ChemComp-NDP: ![]() ChemComp-NAP: ![]() ChemComp-CO8: ![]() ChemComp-COO: |
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