Saket R Bagde / Irimpan I Mathews / J Christopher Fromme / Chu-Young Kim /
PubMed Abstract
Type I modular polyketide synthases are homodimeric multidomain assembly line enzymes that synthesize a variety of polyketide natural products by performing polyketide chain extension and β-keto ...Type I modular polyketide synthases are homodimeric multidomain assembly line enzymes that synthesize a variety of polyketide natural products by performing polyketide chain extension and β-keto group modification reactions. We determined the 2.4-angstrom-resolution x-ray crystal structure and the 3.1-angstrom-resolution cryo–electron microscopy structure of the Lsd14 polyketide synthase, stalled at the transacylation and condensation steps, respectively. These structures revealed how the constituent domains are positioned relative to each other, how they rearrange depending on the step in the reaction cycle, and the specific interactions formed between the domains. Like the evolutionarily related mammalian fatty acid synthase, Lsd14 contains two reaction chambers, but only one chamber in Lsd14 has the full complement of catalytic domains, indicating that only one chamber produces the polyketide product at any given time.
EMDB-24862: CryoEM structure of modular PKS holo-Lsd14 bound to antibody fragment 1B2, stalled at the condensation step, consensus refinement Method: EM (single particle) / Resolution: 3.1 Å
EMDB-24863: CryoEM map of modular PKS holo-Lsd14 bound to antibody fragment 1B2, stalled at the condensation step, focused refinement of KS-KS'-ACP domains Method: EM (single particle) / Resolution: 3.2 Å
EMDB-24864: CryoEM map of modular PKS holo-Lsd14 bound to antibody fragment 1B2, stalled at the condensation step, focused refinement of LDAT domains Method: EM (single particle) / Resolution: 3.1 Å
EMDB-24865: CryoEM map of modular PKS holo-Lsd14 bound to antibody fragment 1B2, stalled at the condensation step, focused refinement of LD'AT' domains Method: EM (single particle) / Resolution: 3.1 Å
EMDB-24866: CryoEM map of modular PKS holo-Lsd14 bound to antibody fragment 1B2, stalled at the condensation step, focused refinement of KR domain Method: EM (single particle) / Resolution: 3.4 Å
EMDB-24867: CryoEM map of modular PKS holo-Lsd14 bound to antibody fragment 1B2, stalled at the condensation step, focused refinement of DD* and 1B2 Method: EM (single particle) / Resolution: 3.4 Å
EMDB-24868, PDB-7s6c: CryoEM structure of modular PKS holo-Lsd14 stalled at the condensation step and bound to antibody fragment 1B2, composite structure Method: EM (single particle) / Resolution: 3.1 Å
EMDB-24869: CryoEM map of modular PKS holo-Lsd14 bound to antibody fragment 1B2, consensus refinement Method: EM (single particle) / Resolution: 3.1 Å
EMDB-24870: CryoEM map of modular PKS holo-Lsd14 bound to antibody fragment 1B2, focused refinement of KSAT dimer Method: EM (single particle) / Resolution: 3.1 Å
EMDB-24871: CryoEM map of modular PKS holo-Lsd14 bound to antibody fragment 1B2, focused refinement of LDAT domains Method: EM (single particle) / Resolution: 3.1 Å
EMDB-24872: CryoEM map of modular PKS holo-Lsd14 bound to antibody fragment 1B2, focused refinement of LD'AT' domains Method: EM (single particle) / Resolution: 3.1 Å
EMDB-24873: CryoEM map of modular PKS holo-Lsd14 bound to antibody fragment 1B2, focused refinement of KR domain Method: EM (single particle) / Resolution: 3.6 Å
EMDB-24874: CryoEM map of modular PKS holo-Lsd14 bound to antibody fragment 1B2, focused refinement of DD* and 1B2 Method: EM (single particle) / Resolution: 3.2 Å
EMDB-24875, PDB-7s6d: CryoEM structure of modular PKS holo-Lsd14 bound to antibody fragment 1B2, composite structure Method: EM (single particle) / Resolution: 3.1 Å
EMDB-24880: CryoEM map of modular PKS apo-Lsd14 bound to antibody fragment 1B2, consensus refinement Method: EM (single particle) / Resolution: 3.4 Å
PDB-7s6b: Crystal structure of modular polyketide synthase apo-Lsd14 from the Lasalocid biosynthesis pathway, trapped in the transacylation step Method: X-RAY DIFFRACTION / Resolution: 2.35 Å
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Keywords
streptomyces lasalocidi (bacteria)
homo sapiens (human)