Structural and dynamical rationale for fatty acid unsaturation in Escherichia coli .

Autor:	Dodge GJ; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-2216.; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216., Patel A; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0340., Jaremko KL; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0340., McCammon JA; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0340; jmccammon@ucsd.edu JanetSmith@umich.edu mburkart@ucsd.edu.; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0340., Smith JL; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-2216; jmccammon@ucsd.edu JanetSmith@umich.edu mburkart@ucsd.edu.; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216., Burkart MD; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0340; jmccammon@ucsd.edu JanetSmith@umich.edu mburkart@ucsd.edu.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Apr 02; Vol. 116 (14), pp. 6775-6783. Date of Electronic Publication: 2019 Mar 14.
DOI:	10.1073/pnas.1818686116
Abstrakt:	Fatty acid biosynthesis in α- and γ-proteobacteria requires two functionally distinct dehydratases, FabA and FabZ. Here, mechanistic cross-linking facilitates the structural characterization of a stable hexameric complex of six Escherichia coli FabZ dehydratase subunits with six AcpP acyl carrier proteins. The crystal structure sheds light on the divergent substrate selectivity of FabA and FabZ by revealing distinct architectures of the binding pocket. Molecular dynamics simulations demonstrate differential biasing of substrate orientations and conformations within the active sites of FabA and FabZ such that FabZ is preorganized to catalyze only dehydration, while FabA is primed for both dehydration and isomerization. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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