PDBsum entry 4zjb

Lyase/biosynthetic protein

PDB id: 4zjb

Contents

Protein chains

150 a.a.

81 a.a.

Ligands

CIT

PNS

Waters ×72

References listed in PDB file

Key reference

• Title: Crystal structure of fabz-Acp complex reveals a dynamic seesaw-Like catalytic mechanism of dehydratase in fatty acid biosynthesis.
• Authors: L.Zhang, J.Xiao, J.Xu, T.Fu, Z.Cao, L.Zhu, H.Z.Chen, X.Shen, H.Jiang, L.Zhang.
• Ref.: Cell Res, 2016, 26, 1330-1344.
• PubMed id: 27874013

Abstract

Fatty 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 Å 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 β-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.