PDBsum entry 2cdh

Transferase

PDB id

2cdh

Contents

			Protein chains

					(+ 0 more) 226 a.a.*


					(+ 6 more) 305 a.a.*


					(+ 0 more) 406 a.a.*


					(+ 0 more) 244 a.a.*


					(+ 0 more) 248 a.a.*

* C-alpha coords only

References listed in PDB file

Key reference

Title

Architecture of a fungal fatty acid synthase at 5 a resolution.

Authors

S.Jenni, M.Leibundgut, T.Maier, N.Ban.

Ref.

Science, 2006, 311, 1263-1267. [DOI no: 10.1126/science.1123251]

PubMed id

16513976

Abstract

All steps of fatty acid synthesis in fungi are catalyzed by the fatty acid synthase, which forms a 2.6-megadalton alpha6beta6 complex. We have determined the molecular architecture of this multienzyme by fitting the structures of homologous enzymes that catalyze the individual steps of the reaction pathway into a 5 angstrom x-ray crystallographic electron density map. The huge assembly contains two separated reaction chambers, each equipped with three sets of active sites separated by distances up to approximately 130 angstroms, across which acyl carrier protein shuttles substrates during the reaction cycle. Regions of the electron density arising from well-defined structural features outside the catalytic domains separate the two reaction chambers and serve as a matrix in which domains carrying the various active sites are embedded. The structure rationalizes the compartmentalization of fatty acid synthesis, and the spatial arrangement of the active sites has specific implications for our understanding of the reaction cycle mechanism and of the architecture of multienzymes in general.



	Figure 4. Fig. 4. The 5 Å electron density map of the fungal FAS. (A) Side view of the electron density along one of the twofold axes of FAS, contoured at 1.8 . The density is colored according to the fitted domains, using the color scheme described in (C). Regions of electron density not corresponding to homologous domains are colored white, including the unassigned domain at the end of the 50 Å–long helix that occludes one of the two large side openings. (B) Top view of the central wheel, which divides the interior of the FAS assembly into two reaction chambers. The KS and KR domains occupy only part of the electron density and are colored orange and yellow, respectively. Additional structural features involved in the formation of the FAS complex are shown in white. Spokes of electron density extend from the central hub of the wheel to the periphery. Bundles of helices connect the KS and KR. (C) Arrangement of the different catalytic domains in the multienzyme complex. To illustrate the localization, the domains are mapped onto the cryoelectron microscopy reconstruction (12). KS is colored orange, KR yellow, MPT red, DH light green, ER dark green, and AT magenta. (D) Distribution of the and ß chains in the FAS complex. Electron density belonging to the chain that forms the central wheel is shown in blue, the density of the ß chain that folds into the arches on both sides of the FAS particle is in green, and the currently unassigned density is in white.		Figure 5. Fig. 5. (A) All active sites of the fungal FAS are oriented toward the interior of the reaction chamber. The dome (lower panel) is cut from the central wheel (upper panel) and flipped open. Fitted domains are colored in light brown and unassigned electron density is in gray. The trimeric connection at the apices of the particle observed in the 8 Å–resolution map is also shown in gray. Red cones indicate the entrances to the hydrophobic clefts that lead to the active sites. (B) Set of active sites in the reaction chamber with all enzymatic activities required for the fatty acid synthesis cycle. The view is into the reaction chamber, with one-third of the dome removed. Distances between the central structural feature (indicated by green spheres) and the active sites are indicated with red lines. (C) Schematic path of ACP, shown as a gray sphere, during substrate shuttling between the active sites.

	Headers