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Crystal structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase(FabZ) in complex with holo-ACP from Helicobacter pyloriCrystal structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase(FabZ) in complex with holo-ACP from Helicobacter pylori
Structural highlights
FunctionQ5G940_HELPX Involved in unsaturated fatty acids biosynthesis. Catalyzes the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs.[HAMAP-Rule:MF_00406] Involved in unsaturated fatty acids biosynthesis. Catalyzes the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs (By similarity).[SAAS:SAAS00205551] Publication Abstract from PubMedFatty acid biosynthesis (FAS) is a vital process in cells. Fatty acids are essential for cell assembly and cellular metabolism. Abnormal FAS directly correlates with cell growth delay and human diseases, such as metabolic syndromes and various cancers. The FAS system utilizes an acyl carrier protein (ACP) as a transporter to stabilize and shuttle the growing fatty acid chain throughout enzymatic modules for stepwise catalysis. Studying the interactions between enzymatic modules and ACP is, therefore, critical for understanding the biological function of the FAS system. However, the information remains unclear due to the high flexibility of ACP and its weak interaction with enzymatic modules. We present here a 2.55 A crystal structure of type II FAS dehydratase FabZ in complex with holo-ACP, which exhibits a highly symmetrical FabZ hexamer-ACP3 stoichiometry with each ACP binding to a FabZ dimer subunit. Further structural analysis, together with biophysical and computational results, reveals a novel dynamic seesaw-like ACP binding and catalysis mechanism for the dehydratase module in the FAS system, which is regulated by a critical gatekeeper residue (Tyr100 in FabZ) that manipulates the movements of the beta-sheet layer. These findings improve the general understanding of the dehydration process in the FAS system and will potentially facilitate drug and therapeutic design for diseases associated with abnormalities in FAS. Crystal structure of FabZ-ACP complex reveals a dynamic seesaw-like catalytic mechanism of dehydratase in fatty acid biosynthesis.,Zhang L, Xiao J, Xu J, Fu T, Cao Z, Zhu L, Chen HZ, Shen X, Jiang H, Zhang L Cell Res. 2016 Dec;26(12):1330-1344. doi: 10.1038/cr.2016.136. Epub 2016 Nov 22. PMID:27874013[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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