PDBsum entry 2uv8

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Transferase PDB id
Protein chains
1614 a.a.
2033 a.a.
FMN ×3

References listed in PDB file
Key reference
Title Structural basis for substrate delivery by acyl carrier protein in the yeast fatty acid synthase.
Authors M.Leibundgut, S.Jenni, C.Frick, N.Ban.
Ref. Science, 2007, 316, 288-290. [DOI no: 10.1126/science.1138249]
PubMed id 17431182
In the multifunctional fungal fatty acid synthase (FAS), the acyl carrier protein (ACP) domain shuttles reaction intermediates covalently attached to its prosthetic phosphopantetheine group between the different enzymatic centers of the reaction cycle. Here, we report the structure of the Saccharomyces cerevisiae FAS determined at 3.1 angstrom resolution with its ACP stalled at the active site of ketoacyl synthase. The ACP contacts the base of the reaction chamber through conserved, charge-complementary surfaces, which optimally position the ACP toward the catalytic cleft of ketoacyl synthase. The conformation of the prosthetic group suggests a switchblade mechanism for acyl chain delivery to the active site of the enzyme.
Figure 2.
Fig. 2. Structure of yeast ACP bound to the KS catalytic cleft. (A) The prosthetic PPT group (spheres) covalently attached to the ACP core (cyan) adopts an extended conformation in the fungal FAS complex. The ACP core forms a compact domain with an additional four-helix bundle (gray), rendering fungal ACP considerably larger than the bacterial counterpart (blue, shown in the same orientation). During interdomain substrate shuttling, the PTT arm might fold back on ACP (arrow), thereby inserting the acyl chain into a cavity formed by the ACP core, as observed in the isolated E. coli ACP structure (16). (B) Detailed view of PPT bound in the catalytic cleft of KS. The unbiased threefold averaged F[obs] – F[calc] simulated annealing omit map (green) shows ACP and the phosphate and pantoic acid (PA) moieties of the PPT prosthetic group. Modeling of the additional PPT part shows that the catalytic residues of KS can easily be reached. KS1 and KS2 form the dimer to which ACP is bound.
Figure 3.
Fig. 3. Mode of ACP binding to the central wheel and the catalytic cleft entrance of KS (gray). (A) The extended prosthetic PPT group (magenta) of ACP (cyan) reaches into the catalytic pocket of KS (asterisk). Distal to the PPT arm, ACP is flexibly tethered to the central hub (green dot) and the peripheral anchor (dashed circle) at the interior of the dome (brown). (B) Top and bottom views of ACP bound to the entrance cleft of KS via its core part and contacting the central wheel with the additional part. (C) ACP binding is mediated by complementarily charged patches, as visualized by the electrostatic surface potential of the contact areas (blue, positive; red, negative).
The above figures are reprinted by permission from the AAAs: Science (2007, 316, 288-290) copyright 2007.
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