Crystal structures of dehydratase domains from the curacin polyketide biosynthetic pathway.

Crystal structures of dehydratase domains from the curacin polyketide biosynthetic pathway.
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DOI:
10.1016/j.str.2009.10.018
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发表时间:
2010-01-13
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Smith JL
Smith JL
中科院分区:
其他
文献类型:
--
作者:
Akey DL;Razelun JR;Tehranisa J;Sherman DH;Gerwick WH;Smith JL

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Modular polyketide synthases (PKS) make novel natural products through a series of pre-programmed chemical steps catalyzed by an assembly line of multi-domain modules. Each assembly line step involves unique extension and modification reactions, resulting in tremendous diversity of polyketide products. Dehydratase domains catalyze formation of an α,β-double bond in the nascent polyketide intermediate. We present crystal structures of the four dehydratase domains from the curacin A PKS. The catalytic residues and substrate binding site reside in a tunnel within a single monomer. The positions of the catalytic residues and shape of the substrate tunnel explain how chirality of the substrate hydroxyl group may determine the configuration of the product double bond. Access to the active site may require opening the substrate tunnel, forming an open trench. The arrangement of monomers within the dimer is consistent among PKS dehydratases and differs from that seen in the related mammalian fatty acid synthases.
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