PDBsum entry 6rvb

Oxidoreductase

PDB id: 6rvb

Contents

Protein chains

443 a.a.

Ligands

FAD ×4

NAD ×4

COA ×4

Waters ×112

References listed in PDB file

Key reference

• Title: Characterization and X-Ray structure of the nadh-Dependent coenzyme a disulfide reductase from thermus thermophilus.
• Authors: A.M.Lencina, J.Koepke, J.Preu, C.Muenke, R.B.Gennis, H.Michel, L.A.Schurig-Briccio.
• Ref.: Biochim Biophys Acta Bioenerg, 2019, 1860, 148080. [DOI no: 10.1016/j.bbabio.2019.148080]
• PubMed id: 31520616

Abstract

The crystal structure of the enzyme previously characterized as a type-2 NADH:menaquinone oxidoreductase (NDH-2) from Thermus thermophilus has been solved at a resolution of 2.9 Å and revealed that this protein is, in fact, a coenzyme A-disulfide reductase (CoADR). Coenzyme A (CoASH) replaces glutathione as the major low molecular weight thiol in Thermus thermophilus and is maintained in the reduced state by this enzyme (CoADR). Although the enzyme does exhibit NADH:menadione oxidoreductase activity expected for NDH-2 enzymes, the specific activity with CoAD as an electron acceptor is about 5-fold higher than with menadione. Furthermore, the crystal structure contains coenzyme A covalently linked Cys44, a catalytic intermediate (Cys44-S-S-CoA) reduced by NADH via the FAD cofactor. Soaking the crystals with menadione shows that menadione can bind to a site near the redox active FAD, consistent with the observed NADH:menadione oxidoreductase activity. CoADRs from other species were also examined and shown to have measurable NADH:menadione oxidoreductase activity. Although a common feature of this family of enzymes, no biological relevance is proposed. The CoADR from T. thermophilus is a soluble homodimeric enzyme. Expression of the recombinant TtCoADR at high levels in E. coli results in a small fraction that co-purifies with the membrane fraction, which was used previously to isolate the enzyme wrongly identified as a membrane-bound NDH-2. It is concluded that T. thermophilus does not contain an authentic NDH-2 component in its aerobic respiratory chain.