| Structural highlights
Function
[PAAZ_ECOLI] Catalyzes the hydrolytic ring cleavage of 2-oxepin-2(3H)-ylideneacetyl-CoA (oxepin-CoA) via the open-chain aldehyde intermediate to yield 3-oxo-5,6-dehydrosuberyl-CoA. The enzyme consists of a C-terminal (R)-specific enoyl-CoA hydratase domain (formerly MaoC) that cleaves the ring and produces the highly reactive 3-oxo-5,6-dehydrosuberyl-CoA semialdehyde and an N-terminal NADP-dependent aldehyde dehydrogenase domain that oxidizes the aldehyde to 3-oxo-5,6-dehydrosuberyl-CoA. Can also use crotonyl-CoA as substrate.[1] [2] [3]
Publication Abstract from PubMed
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.
Molecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway.,Sathyanarayanan N, Cannone G, Gakhar L, Katagihallimath N, Sowdhamini R, Ramaswamy S, Vinothkumar KR Nat Commun. 2019 Sep 11;10(1):4127. doi: 10.1038/s41467-019-11931-1. PMID:31511507[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Teufel R, Mascaraque V, Ismail W, Voss M, Perera J, Eisenreich W, Haehnel W, Fuchs G. Bacterial phenylalanine and phenylacetate catabolic pathway revealed. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14390-5. doi:, 10.1073/pnas.1005399107. Epub 2010 Jul 21. PMID:20660314 doi:10.1073/pnas.1005399107
- ↑ Teufel R, Gantert C, Voss M, Eisenreich W, Haehnel W, Fuchs G. Studies on the mechanism of ring hydrolysis in phenylacetate degradation: a metabolic branching point. J Biol Chem. 2011 Apr 1;286(13):11021-34. doi: 10.1074/jbc.M110.196667. Epub 2011, Feb 4. PMID:21296885 doi:http://dx.doi.org/10.1074/jbc.M110.196667
- ↑ Ferrandez A, Minambres B, Garcia B, Olivera ER, Luengo JM, Garcia JL, Diaz E. Catabolism of phenylacetic acid in Escherichia coli. Characterization of a new aerobic hybrid pathway. J Biol Chem. 1998 Oct 2;273(40):25974-86. PMID:9748275
- ↑ Sathyanarayanan N, Cannone G, Gakhar L, Katagihallimath N, Sowdhamini R, Ramaswamy S, Vinothkumar KR. Molecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway. Nat Commun. 2019 Sep 11;10(1):4127. doi: 10.1038/s41467-019-11931-1. PMID:31511507 doi:http://dx.doi.org/10.1038/s41467-019-11931-1
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