Protein Family Models

Glutathione biosynthesis is achieved in most organisms via a conserved two-step approach relying on the capacity of two independent and unrelated ligases to perform peptide synthesis coupled to ATP hydrolysis. In a first and rate-limiting step, gamma-glutamylcysteine ligase (gamma-ECL) (or GshA; EC:6.3.2.2) uses l-glutamate and l-cysteine to form gamma-glutamylcysteine (gamma-EC), which, in a second step, is condensed with glycine to glutathione by glutathione synthetase (GS) (or GshB; EC:6.3.2.3). However, several pathogenic and free-living bacteria carry out glutathione biosynthesis based on a single enzyme that catalyzes both the gamma-ECL and the GS reactions. Such bifunctional glutathione-synthesizing enzymes have been termed gamma-GCS-GS or GshF [1]. Hybrid GshF contains a typical gamma-proteobacterial gamma-ECL fused to an ATP-grasp-like domain [2]. The ATP-grasp-like module is responsible for the ensuing formation of glutathione from gamma-glutamylcysteine and glycine. The ATP-grasp-like domain has an antiparallel beta-sheet in the GshF structures in contrast to all structurally characterized members of the ATP-grasp superfamily [1]. [1]. 22226834. Glutathione biosynthesis in bacteria by bifunctional GshF is driven by a modular structure featuring a novel hybrid ATP-grasp fold. Stout J, De Vos D, Vergauwen B, Savvides SN;. J Mol Biol. 2012;416:486-494. [2]. 16339152. Characterization of the bifunctional gamma-glutamate-cysteine ligase/glutathione synthetase (GshF) of Pasteurella multocida. Vergauwen B, De Vos D, Van Beeumen JJ;. J Biol Chem. 2006;281:4380-4394. (from Pfam)

Date:

2024-10-16

This ATP-grasp domain is found in the ribosomal S6 modification enzyme RimK [1]. [1]. 9416615. A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity. Galperin MY, Koonin EV;. Protein Sci 1997;6:2639-2643. (from Pfam)

Date:

2024-10-16

This family represents the C-terminal, catalytic domain of the D-alanine--D-alanine ligase enzyme EC:6.3.2.4. D-Alanine is one of the central molecules of the cross-linking step of peptidoglycan assembly. There are three enzymes involved in the D-alanine branch of peptidoglycan biosynthesis: the pyridoxal phosphate-dependent D-alanine racemase (Alr), the ATP-dependent D-alanine:D-alanine ligase (Ddl), and the ATP-dependent D-alanine:D-alanine-adding enzyme (MurF) [3]. [1]. 9054558. D-alanine:D-alanine ligase: phosphonate and phosphinate intermediates with wild type and the Y216F mutant. Fan C, Park IS, Walsh CT, Knox JR;. Biochemistry 1997;36:2531-2538. [2]. 10908650. The molecular basis of vancomycin resistance in clinically relevant Enterococci: crystal structure of D-alanyl-D-lactate ligase (VanA). Roper DI, Huyton T, Vagin A, Dodson G;. Proc Natl Acad Sci U S A 2000;97:8921-8925. [3]. 12499203. Roles of Mycobacterium smegmatis D-alanine:D-alanine ligase and D-alanine racemase in the mechanisms of action of and resistance to the peptidoglycan inhibitor D-cycloserine. Feng Z, Barletta RG;. Antimicrob Agents Chemother 2003;47:283-291. (from Pfam)

Date:

2024-10-16

Phosphoribosylglycinamide synthetase catalyses the second step in the de novo biosynthesis of purine. The reaction catalysed by Phosphoribosylglycinamide synthetase is the ATP- dependent addition of 5-phosphoribosylamine to glycine to form 5'phosphoribosylglycinamide. This domain is related to the ATP-grasp domain of biotin carboxylase/carbamoyl phosphate synthetase (see Pfam:PF02786). [1]. 2687276. Nucleotide sequence analysis of genes purH and purD involved in the de novo purine nucleotide biosynthesis of Escherichia coli. Aiba A, Mizobuchi K;. J Biol Chem 1989;264:21239-21246. [2]. 9843369. X-ray crystal structure of glycinamide ribonucleotide synthetase from Escherichia coli. Wang W, Kappock TJ, Stubbe J, Ealick SE;. Biochemistry 1998;37:15647-15662. (from Pfam)

Date:

2024-10-16

Synthesizes glutathione from L-glutamate and L-cysteine via gamma-L-glutamyl-L-cysteine

Gene:

gshAB

Date:

2021-09-20