3TFZ

Crystal structure of Zhui aromatase/cyclase from Streptomcyes sp. R1128

Summary for 3TFZ

• Entry DOI: 10.2210/pdb3tfz/pdb
• Descriptor: Cyclase, POTASSIUM ION, 3-CYCLOHEXYL-1-PROPYLSULFONIC ACID, ... (4 entities in total)
• Functional Keywords: helix-grip, bet v1-like superfamily, aromatic polyketide cyclase/dehydrase, biosynthetic protein
• Biological source: Streptomyces sp. R1128
• Total number of polymer chains: 6
• Total formula weight: 114500.08

Authors

Ames, B.D.,Lee, M.Y.,Moody, C.,Zhang, W.,Tang, Y.,Wong, S.K.,Tsai, S.C. (deposition date: 2011-08-16, release date: 2011-09-14, Last modification date: 2024-02-28)

Primary citation

Ames, B.D.,Lee, M.Y.,Moody, C.,Zhang, W.,Tang, Y.,Tsai, S.C.
Structural and Biochemical Characterization of ZhuI Aromatase/Cyclase from the R1128 Polyketide Pathway.
Biochemistry, 50:8392-8406, 2011

PubMed Abstract: Aromatic polyketides comprise an important class of natural products that possess a wide range of biological activities. The cyclization of the polyketide chain is a critical control point in the biosynthesis of aromatic polyketides. The aromatase/cyclases (ARO/CYCs) are an important component of the type II polyketide synthase (PKS) and help fold the polyketide for regiospecific cyclizations of the first ring and/or aromatization, promoting two commonly observed first-ring cyclization patterns for the bacterial type II PKSs: C7-C12 and C9-C14. We had previously reported the crystal structure and enzymological analyses of the TcmN ARO/CYC, which promotes C9-C14 first-ring cyclization. However, how C7-C12 first-ring cyclization is controlled remains unresolved. In this work, we present the 2.4 Å crystal structure of ZhuI, a C7-C12-specific first-ring ARO/CYC from the type II PKS pathway responsible for the production of the R1128 polyketides. Though ZhuI possesses a helix-grip fold shared by TcmN ARO/CYC, there are substantial differences in overall structure and pocket residue composition that may be important for directing C7-C12 (rather than C9-C14) cyclization. Docking studies and site-directed mutagenesis coupled to an in vitro activity assay demonstrate that ZhuI pocket residues R66, H109, and D146 are important for enzyme function. The ZhuI crystal structure helps visualize the structure and putative dehydratase function of the didomain ARO/CYCs from KR-containing type II PKSs. The sequence-structure-function analysis described for ZhuI elucidates the molecular mechanisms that control C7-C12 first-ring polyketide cyclization and builds a foundation for future endeavors into directing cyclization patterns for engineered biosynthesis of aromatic polyketides.

PubMed: 21870821
DOI: 10.1021/bi200593m

Experimental method

X-RAY DIFFRACTION (2.39 Å)