5NO5

AbyA5 Wildtype

Summary for 5NO5

• Entry DOI: 10.2210/pdb5no5/pdb
• Related: 4YWF
• Descriptor: AbyA5 (2 entities in total)
• Functional Keywords: deacetylase, elimination, hydrolase, spirotetronate, acetyl lyase
• Biological source: Verrucosispora
• Total number of polymer chains: 2
• Total formula weight: 81553.97

Authors

Byrne, M.J.,Race, P.R. (deposition date: 2017-04-10, release date: 2018-05-16, Last modification date: 2024-01-17)

Primary citation

Lees, N.R.,Han, L.C.,Byrne, M.J.,Davies, J.A.,Parnell, A.E.,Moreland, P.E.J.,Stach, J.E.M.,van der Kamp, M.W.,Willis, C.L.,Race, P.R.
An Esterase-like Lyase Catalyzes Acetate Elimination in Spirotetronate/Spirotetramate Biosynthesis.
Angew.Chem.Int.Ed.Engl., 58:2305-2309, 2019

PubMed Abstract: Spirotetronate and spirotetramate natural products include a multitude of compounds with potent antimicrobial and antitumor activities. Their biosynthesis incorporates many unusual biocatalytic steps, including regio- and stereo-specific modifications, cyclizations promoted by Diels-Alderases, and acetylation-elimination reactions. Here we focus on the acetate elimination catalyzed by AbyA5, implicated in the formation of the key Diels-Alder substrate to give the spirocyclic system of the antibiotic abyssomicin C. Using synthetic substrate analogues, it is shown that AbyA5 catalyzes stereospecific acetate elimination, establishing the (R)-tetronate acetate as a biosynthetic intermediate. The X-ray crystal structure of AbyA5, the first of an acetate-eliminating enzyme, reveals a deviant acetyl esterase fold. Molecular dynamics simulations and enzyme assays show the use of a His-Ser dyad to catalyze either elimination or hydrolysis, via disparate mechanisms, under substrate control.

PubMed: 30664319
DOI: 10.1002/anie.201812105

Experimental method

X-RAY DIFFRACTION (2.5 Å)