PDBsum entry 4wys

Transferase

PDB id: 4wys

Contents

Protein chains

396 a.a.

Waters ×692

References listed in PDB file

Key reference

• Title: Redox-Switch regulatory mechanism of thiolase from clostridium acetobutylicum.
• Authors: S.Kim, Y.S.Jang, S.C.Ha, J.W.Ahn, E.J.Kim, J.H.Lim, C.Cho, Y.S.Ryu, S.K.Lee, S.Y.Lee, K.J.Kim.
• Ref.: Nat Commun, 2015, 6, 8410. [DOI no: 10.1038/ncomms9410]
• PubMed id: 26391388

Abstract

Thiolase is the first enzyme catalysing the condensation of two acetyl-coenzyme A (CoA) molecules to form acetoacetyl-CoA in a dedicated pathway towards the biosynthesis of n-butanol, an important solvent and biofuel. Here we elucidate the crystal structure of Clostridium acetobutylicum thiolase (CaTHL) in its reduced/oxidized states. CaTHL, unlike those from other aerobic bacteria such as Escherichia coli and Zoogloea ramegera, is regulated by the redox-switch modulation through reversible disulfide bond formation between two catalytic cysteine residues, Cys88 and Cys378. When CaTHL is overexpressed in wild-type C. acetobutylicum, butanol production is reduced due to the disturbance of acidogenic to solventogenic shift. The CaTHL(V77Q/N153Y/A286K) mutant, which is not able to form disulfide bonds, exhibits higher activity than wild-type CaTHL, and enhances butanol production upon overexpression. On the basis of these results, we suggest that CaTHL functions as a key enzyme in the regulation of the main metabolism of C. acetobutylicum through a redox-switch regulatory mechanism.