5ZK4

The structure of DSZS acyltransferase with carrier protein

Summary for 5ZK4

• Entry DOI: 10.2210/pdb5zk4/pdb
• Descriptor: DisD protein, DisA protein, SULFATE ION, ... (5 entities in total)
• Functional Keywords: transferase, acyl carrier protein, polyketide biosynthesis
• Biological source: Sorangium cellulosum (Polyangium cellulosum); More
• Total number of polymer chains: 4
• Total formula weight: 88670.28

Authors

Miyanaga, A.,Ouchi, R.,Kudo, F.,Eguchi, T. (deposition date: 2018-03-23, release date: 2018-06-13, Last modification date: 2024-11-13)

Primary citation

Miyanaga, A.,Ouchi, R.,Ishikawa, F.,Goto, E.,Tanabe, G.,Kudo, F.,Eguchi, T.
Structural basis of protein-protein interactions between a trans-acting acyltransferase and acyl carrier protein in polyketide disorazole biosynthesis
J. Am. Chem. Soc., 140:7970-7978, 2018

PubMed Abstract: Acyltransferases (ATs) are responsible for the selection and incorporation of acyl building blocks in the biosynthesis of various polyketide natural products. The trans-AT modular polyketide synthases have a discrete trans-acting AT for the loading of an acyl unit onto the acyl carrier protein (ACP) located within each module. Despite the importance of protein-protein interactions between ATs and ACPs in trans-AT assembly lines, the dynamic actions of ACPs and trans-acting ATs remain largely uncharacterized because of the inherently transient nature of ACP-enzyme interactions. Herein, we report the crystal structure of the AT-ACP complex of disorazole trans-AT polyketide synthase. We used a bromoacetamide pantetheine cross-linking probe in combination with a Cys mutation to trap the transient AT-ACP complex, allowing the determination of the crystal structure of the disorazole AT-ACP complex at 2.03 Å resolution. On the basis of the cross-linked AT-ACP complex structure, ACP residues recognized by trans-acting AT were identified and validated by mutational studies, which demonstrated that the disorazole AT recognizes the loop 1 and helix III' residues of disorazole ACP. The disorazole AT-ACP complex structure presents a foundation for defining the dynamic processes associated with trans-acting ATs and provides detailed mechanistic insights into their ability to recognize ACPs.

PubMed: 29870659
DOI: 10.1021/jacs.8b04162

Experimental method

X-RAY DIFFRACTION (2.03 Å)