Steve Ealick's Research Group
Streptomyces sahachiroi AziG
5HMC 5-methyl naphthoic acid complex.
The azinomycins are a family of potent antitumor agents with the ability to form interstrand crosslinks with DNA. AziG is a thioesterase that acts as a chain elongation and cyclization (CEC) domain and is required for the additional two rounds of chain extension to form the
final azinomycin product.
|The monomer adopts the characteristic thioesterase domain hotdog fold with the β-sheet of each monomer facing the core and the main α-helices facing outward.|
AziG forms a tetramer with four 5-methylnaphthoic acid binding sites at the interface of two AziG chains. Each cavity is approximately 7 Å in diameter and 20 Å deep.
The AziG/5-methylnaphthoic acid bound structure enables us to identify possible catalytic residues and propose a mechanism for the reaction.
Mori S, Simkhada D, Zhang H, Erb MS, Zhang Y, Williams HJ, Fedoseyenko D, Russell WK, Kim D, Fleer N, Ealick SE, and Watanabe CM. Polyketide Ring Expansion Mediated by a Thioesterase, CEC Domain, in Azinomycin Biosynthesis: Characterization of AziB and AziG. Biochemistry 55:704-714 (2016). PubMed