Structural and dynamical rationale for fatty acid unsaturation in Escherichia coli

Dodge, Greg J.; Patel, Ashay; Jaremko, Kara L.; McCammon, J. Andrew; Smith, Janet L.; Burkart, Michael D.

doi:10.1073/pnas.1818686116

Structural and dynamical rationale for fatty acid unsaturation in Escherichia coli

Journal Article · Thu Mar 14 00:00:00 EDT 2019 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1818686116· OSTI ID:1558325

Dodge, Greg J. ^[1]; ^[2]; Jaremko, Kara L. ^[2]; McCammon, J. Andrew ^[2]; Smith, Janet L. ^[1]; Burkart, Michael D. ^[2]

Univ. of Michigan, Ann Arbor, MI (United States)
Univ. of California, San Diego, La Jolla CA (United States)

Fatty acid biosynthesis in α- and γ-proteobacteria requires two functionally distinct dehydratases, FabA and FabZ. In this work, mechanistic cross-linking facilitates the structural characterization of a stable hexameric complex of six Escherichia coliFabZ 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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Cancer Institute (NCI); National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1558325

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 14 Vol. 116; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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