6SJ0

Amidohydrolase, AHS

Summary for 6SJ0

• Entry DOI: 10.2210/pdb6sj0/pdb
• Descriptor: Amidohydrolase, BICARBONATE ION, SULFATE ION, ... (6 entities in total)
• Functional Keywords: paak like ligase, hydrolase
• Biological source: Streptomyces sp.
• Total number of polymer chains: 2
• Total formula weight: 114599.53

Authors

Naismith, J.H.,Song, H. (deposition date: 2019-08-12, release date: 2020-01-15, Last modification date: 2024-05-15)

Primary citation

Song, H.,Rao, C.,Deng, Z.,Yu, Y.,Naismith, J.H.
The Biosynthesis of the Benzoxazole in Nataxazole Proceeds via an Unstable Ester and has Synthetic Utility.
Angew.Chem.Int.Ed.Engl., 59:6054-6061, 2020

PubMed Abstract: Heterocycles, a class of molecules that includes oxazoles, constitute one of the most common building blocks in current pharmaceuticals and are common in medicinally important natural products. The antitumor natural product nataxazole is a model for a large class of benzoxazole-containing molecules that are made by a pathway that is not characterized. We report structural, biochemical, and chemical evidence that benzoxazole biosynthesis proceeds through an ester generated by an ATP-dependent adenylating enzyme. The ester rearranges via a tetrahedral hemiorthoamide to yield an amide, which is a shunt product and not, as previously thought, an intermediate in the pathway. A second zinc-dependent enzyme catalyzes the formation of hemiorthoamide from the ester but, by shuttling protons, the enzyme eliminates water, a reverse hydrolysis reaction, to yield the benzoxazole and avoids the amide. These insights have allowed us to harness the pathway to synthesize a series of novel halogenated benzoxazoles.

PubMed: 31903677
DOI: 10.1002/anie.201915685

Experimental method

X-RAY DIFFRACTION (1.75 Å)