PDBsum entry 4xom

Unknown function

PDB id: 4xom

Contents

Protein chains

206 a.a.

193 a.a.

178 a.a.

Ligands

SO4 ×2

Waters ×240

References listed in PDB file

Key reference

• Title: Elongation of the poly-γ-Glutamate tail of f420 requires both domains of the f420:γ-Glutamyl ligase (fbib) of mycobacterium tuberculosis.
• Authors: G.Bashiri, A.M.Rehan, S.Sreebhavan, H.M.Baker, E.N.Baker, C.J.Squire.
• Ref.: J Biol Chem, 2016, 291, 6882-6894. [DOI no: 10.1074/jbc.M115.689026]
• PubMed id: 26861878

Abstract

Cofactor F420is an electron carrier with a major role in the oxidoreductive reactions ofMycobacterium tuberculosis, the causative agent of tuberculosis. A γ-glutamyl ligase catalyzes the final steps of the F420biosynthesis pathway by successive additions ofl-glutamate residues to F420-0, producing a poly-γ-glutamate tail. The enzyme responsible for this reaction in archaea (CofE) comprises a single domain and produces F420-2 as the major species. The homologousM. tuberculosisenzyme, FbiB, is a two-domain protein and produces F420with predominantly 5-7l-glutamate residues in the poly-γ-glutamate tail. The N-terminal domain of FbiB is homologous to CofE with an annotated γ-glutamyl ligase activity, whereas the C-terminal domain has sequence similarity to an FMN-dependent family of nitroreductase enzymes. Here we demonstrate that full-length FbiB adds multiplel-glutamate residues to F420-0in vitroto produce F420-5 after 24 h; communication between the two domains is critical for full γ-glutamyl ligase activity. We also present crystal structures of the C-terminal domain of FbiB in apo-, F420-0-, and FMN-bound states, displaying distinct sites for F420-0 and FMN ligands that partially overlap. Finally, we discuss the features of a full-length structural model produced by small angle x-ray scattering and its implications for the role of N- and C-terminal domains in catalysis.