EMD-23710
6-Deoxyerythronolide B synthase (DEBS) hybrid module (M3/1) in complex with antibody fragment 1B2
EMD-23710
Single-particle3.2 Å
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Map released: 17/11/2021
Last modified: 30/10/2024
Sample Organism:
Saccharopolyspora erythraea,
Homo sapiens
Sample: Complex between DEBS M3/1TE and antibody fragment 1B2
Fitted models: 7m7e (Avg. Q-score: 0.449)
Deposition Authors: Cogan DP
,
Zhang K
Sample: Complex between DEBS M3/1TE and antibody fragment 1B2
Fitted models: 7m7e (Avg. Q-score: 0.449)
Deposition Authors: Cogan DP
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Mapping the catalytic conformations of an assembly-line polyketide synthase module.
Cogan DP
,
Zhang K
,
Li X
,
Li S
,
Pintilie GD
,
Roh SH
,
Craik CS
,
Chiu W
,
Khosla C
(2021) Science , 374 , 729 - 734
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(2021) Science , 374 , 729 - 734
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.
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.