5VCB
Crystal structure of holo-(acyl-carrier-protein) synthase:holo(acyl-carrier-protein) complex from Escherichia Coli.
Summary for 5VCB
| Entry DOI | 10.2210/pdb5vcb/pdb |
| Descriptor | Holo-[acyl-carrier-protein] synthase, Acyl carrier protein, 4'-PHOSPHOPANTETHEINE (3 entities in total) |
| Functional Keywords | hexamer product complex, transferase |
| Biological source | Escherichia coli (strain K12) More |
| Total number of polymer chains | 30 |
| Total formula weight | 346669.01 |
| Authors | Marcella, A.M.,Barb, A.W. (deposition date: 2017-03-31, release date: 2017-11-01, Last modification date: 2023-10-04) |
| Primary citation | Marcella, A.M.,Culbertson, S.J.,Shogren-Knaak, M.A.,Barb, A.W. Structure, High Affinity, and Negative Cooperativity of the Escherichia coli Holo-(Acyl Carrier Protein):Holo-(Acyl Carrier Protein) Synthase Complex. J. Mol. Biol., 429:3763-3775, 2017 Cited by PubMed Abstract: The Escherichia coli holo-(acyl carrier protein) synthase (ACPS) catalyzes the coenzyme A-dependent activation of apo-ACPP to generate holo-(acyl carrier protein) (holo-ACPP) in an early step of fatty acid biosynthesis. E. coli ACPS is sufficiently different from the human fatty acid synthase to justify the development of novel ACPS-targeting antibiotics. Models of E. coli ACPS in unliganded and holo-ACPP-bound forms solved by X-ray crystallography to 2.05and 4.10Å, respectively, revealed that ACPS bound three product holo-ACPP molecules to form a 3:3 hexamer. Solution NMR spectroscopy experiments validated the ACPS binding interface on holo-ACPP using chemical shift perturbations and by determining the relative orientation of holo-ACPP to ACPS by fitting residual dipolar couplings. The binding interface is organized to arrange contacts between positively charged ACPS residues and the holo-ACPP phosphopantetheine moiety, indicating product contains more stabilizing interactions than expected in the enzyme:substrate complex. Indeed, holo-ACPP bound the enzyme with greater affinity than the substrate, apo-ACPP, and with negative cooperativity. The first equivalent of holo-ACPP bound with a K=62±13nM, followed by the binding of two more equivalents of holo-ACPP with K=1.2±0.2μM. Cooperativity was not observed for apo-ACPP which bound with K=2.4±0.1μM. Strong product binding and high levels of holo-ACPP in the cell identify a potential regulatory role of ACPS in fatty acid biosynthesis. PubMed: 29054754DOI: 10.1016/j.jmb.2017.10.015 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (4.1 Å) |
Structure validation
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