6JQL

Structure of PaaZ, a bifunctional enzyme

Summary for 6JQL

• Entry DOI: 10.2210/pdb6jql/pdb
• EMDB information: 9873
• Descriptor: Bifunctional protein PaaZ (1 entity in total)
• Functional Keywords: substrate channeling, bi-functional enzyme, hydrolase, dehydrogenase
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 6
• Total formula weight: 443816.35

Authors

Gakher, L.,Vinothkumar, K.R.,Katagihallimath, N.,Sowdhamini, R.,Sathyanarayanan, N.,Cannone, G. (deposition date: 2019-03-31, release date: 2019-09-11, Last modification date: 2024-03-27)

Primary citation

Sathyanarayanan, N.,Cannone, G.,Gakhar, L.,Katagihallimath, N.,Sowdhamini, R.,Ramaswamy, S.,Vinothkumar, K.R.
Molecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway.
Nat Commun, 10:4127-4127, 2019

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 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.

PubMed: 31511507
DOI: 10.1038/s41467-019-11931-1

Experimental method

ELECTRON MICROSCOPY (2.9 Å)