8G7X

Human fatty acid synthase dehydratase domain

Summary for 8G7X

• Entry DOI: 10.2210/pdb8g7x/pdb
• Descriptor: 3-hydroxyacyl-[acyl-carrier-protein] dehydratase, THIOCYANATE ION, DIMETHYL SULFOXIDE, ... (5 entities in total)
• Functional Keywords: human, fatty acid synthase, dehydratase, lyase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 55790.18

Authors

Akey, D.L.,Konwerski, J.R.,McCullough, T.M.,Smith, J.L. (deposition date: 2023-02-17, release date: 2023-06-07, Last modification date: 2023-09-20)

Primary citation

McCullough, T.M.,Dhar, A.,Akey, D.L.,Konwerski, J.R.,Sherman, D.H.,Smith, J.L.
Structure of a modular polyketide synthase reducing region.
Structure, 31:1109-1120.e3, 2023

PubMed Abstract: The chemical scaffolds of numerous therapeutics are polyketide natural products, many formed by bacterial modular polyketide synthases (PKS). The large and flexible dimeric PKS modules have distinct extension and reducing regions. Structures are known for all individual enzyme domains and several extension regions. Here, we report the structure of the full reducing region from a modular PKS, the ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) domains of module 5 of the juvenimicin PKS. The modular PKS-reducing region has a different architecture than the homologous fatty acid synthase (FAS) and iterative PKS systems in its arrangement of domains and dimer interface. The structure reveals a critical role for linker peptides in the domain interfaces, leading to discovery of key differences in KR domains dependent on module composition. Finally, our studies provide insight into the mechanism underlying modular PKS intermediate shuttling by carrier protein (ACP) domains.

PubMed: 37348494
DOI: 10.1016/j.str.2023.05.019

Experimental method

X-RAY DIFFRACTION (1.815 Å)