7M7E

6-Deoxyerythronolide B synthase (DEBS) hybrid module (M3/1) in complex with antibody fragment 1B2

Summary for 7M7E

• Entry DOI: 10.2210/pdb7m7e/pdb
• EMDB information: 23710 23711 23712 23713 23714 23715
• Descriptor: 6-deoxyerythronolide-B synthase EryA2, modules 3 and 4,EryAI,6-deoxyerythronolide-B synthase EryA3, modules 5 and 6 chimera, 1B2 (heavy chain), 1B2 (light chain) (3 entities in total)
• Functional Keywords: polyketide synthase, antibody fragment, biosynthetic protein-immune system complex, biosynthetic protein/immune system
• Biological source: Saccharopolyspora erythraea (Streptomyces erythraeus); More
• Total number of polymer chains: 4
• Total formula weight: 427834.29

Authors

Cogan, D.P.,Zhang, K.,Chiu, W.,Khosla, C. (deposition date: 2021-03-28, release date: 2021-11-17, Last modification date: 2025-05-14)

Primary citation

Cogan, D.P.,Zhang, K.,Li, X.,Li, S.,Pintilie, G.D.,Roh, S.H.,Craik, C.S.,Chiu, W.,Khosla, C.
Mapping the catalytic conformations of an assembly-line polyketide synthase module.
Science, 374:729-734, 2021

PubMed Abstract: Assembly-line polyketide synthases, such as the 6-deoxyerythronolide B synthase (DEBS), are large enzyme factories prized for their ability to produce specific and complex polyketide products. By channeling protein-tethered substrates across multiple active sites in a defined linear sequence, these enzymes facilitate programmed small-molecule syntheses that could theoretically be harnessed to access countless polyketide product structures. Using cryogenic electron microscopy to study DEBS module 1, we present a structural model describing this substrate-channeling phenomenon. Our 3.2- to 4.3-angstrom-resolution structures of the intact module reveal key domain-domain interfaces and highlight an unexpected module asymmetry. We also present the structure of a product-bound module that shines light on a recently described “turnstile” mechanism for transient gating of active sites along the assembly line.

PubMed: 34735239
DOI: 10.1126/science.abi8358

Experimental method

ELECTRON MICROSCOPY (3.2 Å)