MF7000995 F420-gamma glutamyl ligase (Archaeoglobus fulgidus) 2phn X-ray 1.35 Homodimer Archaeoglobus fulgidus 17669425 Nocek B, Evdokimova E, Proudfoot M, Kudritska M, Grochowski LL, White RH, Savchenko A, Yakunin AF, Edwards A, Joachimiak A J. Mol. Biol. 2007 2 372 456-69 F(420) is a flavin-like redox-active coenzyme commonly used by archaea and some eubacteria in a variety of biochemical reactions in methanogenesis, the formation of secondary metabolites, the degradation of nitroaromatic compounds, activation of nitroimidazofurans, and F(420)-dependent photolysis in DNA repair. Coenzyme F(420)-2 biosynthesis from 7,8-didemethyl-8-hydroxy-5-deazariboflavin (Fo) and lactaldehyde involves six enzymatic steps and five proteins (CofA, CofB, CofC, CofD, and CofE). CofE, a F(420)-0:gamma-glutamyl ligase, is responsible for the last two enzymatic steps; it catalyses the GTP-dependent addition of two L-glutamate residues to F(420)-0 to form F(420)-2. CofE is found in archaea, the aerobic actinomycetes, and cyanobacteria. Here, we report the first crystal structure of the apo-F(420)-0:gamma-glutamyl ligase (CofE-AF) from Archaeoglobus fulgidus and its complex with GDP at 2.5 A and 1.35 A resolution, respectively. The structure of CofE-AF reveals a novel protein fold with an intertwined, butterfly-like dimer formed by two-domain monomers. GDP and Mn(2+) are bound within the putative active site in a large groove at the dimer interface. We show that the enzyme adds a glutamate residue to both F(420)-0 and F(420)-1 in two distinct steps. CofE represents the first member of a new structural family of non-ribosomal peptide synthases. GO:0052618 coenzyme F420-0 GO:0052619 coenzyme F420-1 GO:0005525 GTP binding GO:0046872 metal ion binding GO:0052645 F420-0 metabolic process 2 1 Homooligomeric enzymes Homodimeric enzymes All chains according to the most probable oligomerization state stored in PDBe were considered. A Coenzyme F420:L-glutamate ligase Archaeoglobus fulgidus O28028 2 249 99% MRVEVFPVEGLPLIKEGDDLAELISSRVRFEDGDVLVVCSTVISKAEGRIRRLEEFNPSERAKEIAARIGKPAEFVQAVLEESEEVLLDFPFLLVKAKFGNVCVNAGIDASNVEEGSLLLPPLDPDGSAEKLRRRILELTGKRVGVIITDTNGRCFRRGVVGFAIGISGVKAMKDWIGRKDLYGRELEVTVECVADEIAAFANLLMGEGGDGIPAVVVRGLNVAGEGSMEEIYRSEEEDVIRRCLKRCL 249 secondary structure helix 22 29 secondary structure helix 43 50 secondary structure helix 57 59 secondary structure helix 62 73 secondary structure helix 75 85 secondary structure helix 109 111 secondary structure helix 127 144 secondary structure helix 196 210 secondary structure helix 231 235 secondary structure helix 242 252 secondary structure strand 6 10 secondary structure strand 38 42 secondary structure strand 53 55 secondary structure strand 86 91 secondary structure strand 97 100 secondary structure strand 105 107 secondary structure strand 120 122 secondary structure strand 148 157 secondary structure strand 160 171 secondary structure strand 177 178 secondary structure strand 194 195 secondary structure strand 218 222 pfam PF01996 F420-0:Gamma-glutamyl ligase 11 220 B Coenzyme F420:L-glutamate ligase Archaeoglobus fulgidus O28028 1 249 100% MRVEVFPVEGLPLIKEGDDLAELISSRVRFEDGDVLVVCSTVISKAEGRIRRLEEFNPSERAKEIAARIGKPAEFVQAVLEESEEVLLDFPFLLVKAKFGNVCVNAGIDASNVEEGSLLLPPLDPDGSAEKLRRRILELTGKRVGVIITDTNGRCFRRGVVGFAIGISGVKAMKDWIGRKDLYGRELEVTVECVADEIAAFANLLMGEGGDGIPAVVVRGLNVAGEGSMEEIYRSEEEDVIRRCLKRCL 249 secondary structure helix 22 29 secondary structure helix 43 50 secondary structure helix 57 59 secondary structure helix 62 73 secondary structure helix 75 85 secondary structure helix 109 111 secondary structure helix 127 144 secondary structure helix 196 210 secondary structure helix 231 235 secondary structure helix 242 252 secondary structure strand 6 10 secondary structure strand 38 42 secondary structure strand 53 55 secondary structure strand 86 91 secondary structure strand 97 100 secondary structure strand 105 107 secondary structure strand 120 122 secondary structure strand 148 157 secondary structure strand 160 171 secondary structure strand 177 178 secondary structure strand 194 195 secondary structure strand 218 222 pfam PF01996 F420-0:Gamma-glutamyl ligase 11 220 Indirect evidence The full structure participates in mutual synergistic folding. - The F420-gamma glutamyl ligase forms a tightly packed, highly intertwined, butterfly-like dimer formed by two-domain monomers. The dimer interface is very extensive and the putative active site lies in a large groove at the dimer interface. Also, the protein is a dimer in solution (SEC) which is in good agreement with its tight packing (PMID:17669425). A N/A B N/A