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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 10 4127 (2019)
Related entries: 6jql, 6jqn, 6jqo

Cited: 9 times
EuropePMC logo 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.

Reviews - 6jqm mentioned but not cited (1)

  1. Progress in structural and functional study of the bacterial phenylacetic acid catabolic pathway, its role in pathogenicity and antibiotic resistance. Jiao M, He W, Ouyang Z, Shi Q, Wen Y. Front Microbiol 13 964019 (2022)

Articles - 6jqm mentioned but not cited (1)

  1. 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 10 4127 (2019)


Reviews citing this publication (4)

  1. Computational Methods for Single-Particle Electron Cryomicroscopy. Singer A, Sigworth FJ. Annu Rev Biomed Data Sci 3 163-190 (2020)
  2. Bacterial Tropone Natural Products and Derivatives: Overview of their Biosynthesis, Bioactivities, Ecological Role and Biotechnological Potential. Duan Y, Petzold M, Saleem-Batcha R, Teufel R. Chembiochem 21 2384-2407 (2020)
  3. Mechanisms and Effects of Substrate Channelling in Enzymatic Cascades. Kondrat S, von Lieres E. Methods Mol Biol 2487 27-50 (2022)
  4. Structural Characterization of Multienzyme Assemblies: An Overview. Papageorgiou AC. Methods Mol Biol 2487 51-72 (2022)

Articles citing this publication (3)

  1. Five enzymes of the Arg/N-degron pathway form a targeting complex: The concept of superchanneling. Oh JH, Hyun JY, Chen SJ, Varshavsky A. Proc Natl Acad Sci U S A 117 10778-10788 (2020)
  2. Structure determination by cryoEM at 100 keV. McMullan G, Naydenova K, Mihaylov D, Yamashita K, Peet MJ, Wilson H, Dickerson JL, Chen S, Cannone G, Lee Y, Hutchings KA, Gittins O, Sobhy MA, Wells T, El-Gomati MM, Dalby J, Meffert M, Schulze-Briese C, Henderson R, Russo CJ. Proc Natl Acad Sci U S A 120 e2312905120 (2023)
  3. Proteomic analysis of meropenem-induced outer membrane vesicles released by carbapenem-resistant Klebsiella pneumoniae. Fan F, Chen G, Deng S, Wei L. Microbiol Spectr 12 e0291723 (2024)


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