The synthesis and transport of fatty acids and their derivatives in biological systems is frequently dependent on protein carriers that provide for both the solubilization and control of the distribution of hydrophobic compounds. Acyl-Carrier Proteins, ACPs, and their acyl derivatives are members of this class, which function as substrates for most enzymes of the fatty acid synthetase system. We propose a structural investigation of a series of ACPs in an effort to elucidate factors which may influence production and distribution of fatty acids. The structural studies will be undertaken using recently developed two-dimensional NMR methods. High field proton spectra will be assigned and cross-relaxation data on assigned resonances used to extract inter-nuclear distance constraints. Structures matching distance constraints will then be sought using both distance geometry programs and molecular mechanics programs modified to incorporate cross-relaxation distance constraints. Acyl chain placements and motions in these structures will be studied using a variety of heteronuclear spin relaxation experiments and results correlated with variation in suitability of various acyl ACPs as substrates for enzymes of the synthetase system. We expect to make contributions both to an understanding of mechanisms for control of fatty acid distribution and to the development of methods for structural study of macromolecules in general.
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