Acyl carrier protein (ACP) transports the growing fatty acid chain between enzyme domains of fatty acid synthase (FAS) during biosynthesis.1 Because FAS enzymes operate upon ACP-bound acyl groups, ACP must stabilize and transport the growing lipid chain.2 The transient nature of ACP-enzyme interactions imposes a major obstacle to gaining high-resolution structural information about fatty acid biosynthesis, and a new strategy is required to properly study protein-protein interactions. In this work, we describe the application of a mechanism-based probe that allows site-selective covalent crosslinking of AcpP to FabA, the E. coli ACP and fatty acid 3-hydroxyacyl-ACP dehydratase. We report the 1.9 Å crystal structure of the crosslinked AcpP=FabA complex as a homo-dimer, in which AcpP exhibits two different conformations likely representing snapshots of ACP in action: the 4′-phosphopantetheine (PPant) group of AcpP first binds an arginine-rich groove of FabA, followed by an AcpP helical conformational change that locks the AcpP and FabA in place. Residues at the interface of AcpP and FabA are identified and validated by solution NMR techniques, including chemical shift perturbations and RDC measurements. These not only support our interpretation of the crystal structures but also provide an animated view of ACP in action during fatty acid dehydration. Combined with molecular dynamics simulations, we show for the first time that FabA extrudes the sequestered acyl chain from the ACP binding pocket before dehydration by repositioning helix III. Extensive sequence conservation among carrier proteins suggests that the mechanistic insights gleaned from our studies will prove general for fatty acid, polyketide and non-ribosomal biosyntheses. Here the foundation is laid for defining the dynamic action of carrier protein activity in primary and secondary metabolism, providing insight into pathways that can play major roles in the treatment of cancer, obesity and infectious disease.
Cs2CuBr4 is an S = 1/2 quasi-two-dimensional frustrated antiferromagnet with a distorted triangular lattice parallel to the bc-plane. Cs2CuBr4 undergoes magnetic ordering at TN = 1.4 K at zero magnetic field. In the ordered phase below TN, spins lie in a plane that is almost parallel to the bc-plane and form a helical incommensurate structure with ordering vector Õ 0 = (0, 0.575, 0). The incommensurate spin structure arises from the spin frustration on the distorted triangular lattice. The magnetization curve has a plateau at approximately one-third of the saturation magnetization for magnetic field H parallel to the b-and c-axes, while no plateau is observed for H a. The ordering vector Õ 0 increases with increasing magnetic field parallel to the c-axis, and is locked at Õ 0 (0, 2/3, 0) in the plateau region, which indicates that the up-up-down spin structure is realized in the plateau state. The magnetization plateau should be attributed to quantum fluctuation. For H b and H c, the second anomaly suggestive of tiny plateau is observed at roughly two-third of the saturation magnetization. The magnetic field versus temperature diagram is presented. Small amount of Cl − substitution for Br − produces drastic suppression of TN. With increasing Cl − concentration x, the magnetic ordering disappears at x 0.17. It is also observed that in Cs2Cu(Br1−xClx)4 phase transition smears with increasing external field and disappears, irrespective of field direction. This should be attributed to the random field effect.KEYWORDS: Cs2CuBr4, Cs2CuCl4, Cs2Cu(Br1−xClx)4, spin frustration, triangular antiferromagnet, quantum fluctuation, helical magnetic ordering, magnetization plateaus, disorder, random field effect IntroductionTriangular antiferromagnets (TAF) have been of great interest from the viewpoint of the interplay of spin frustration and quantum fluctuation. In most of conventional antiferromagnets, which are described by two-sublattice model, the ground state is determined by the classical energy, and the quantum fluctuation gives only small correction to the ground state energy. On the other hand, in Heisenberg TAF, spins form the 120• structure in the ground state due to the spin frustration. However, in a magnetic field, spin structure of the ground state cannot be uniquely determined by the classical energy only, and thus, the ground state has continuous degeneracy in the magnetic field. No phase transition occurs up to saturation, so that the magnetization curve is monotonic. For quantum Heisenberg TAF with small spin S, the quantum fluctuation plays an important role in determining the ground state, because the quantum fluctuation can remove the continuous degeneracy of the classical ground state. The quantum fluctuation in TAF was discussed using the spin wave theory, which describes the spin system
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