2phn
Crystal structure of an amide bond forming F420-gamma glutamyl ligase from Archaeoglobus fulgidus
Structural highlights
FunctionCOFE_ARCFU Catalyzes the GTP-dependent successive addition of two L-glutamates to the L-lactyl phosphodiester of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (F420-0) to form coenzyme F420-0-glutamyl-glutamate (F420-2), with a gamma-linkage between the two glutamates. May be able to add up to four gamma-linked glutamates, since F420-4 is a species that was isolated from A.fulgidus.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedF(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. Structure of an amide bond forming F(420):gamma-glutamyl ligase from Archaeoglobus fulgidus -- a member of a new family of non-ribosomal peptide synthases.,Nocek B, Evdokimova E, Proudfoot M, Kudritska M, Grochowski LL, White RH, Savchenko A, Yakunin AF, Edwards A, Joachimiak A J Mol Biol. 2007 Sep 14;372(2):456-69. Epub 2007 Jun 29. PMID:17669425[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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