Protein Family Models

Mycothiol-dependent nitroreductase Rv2466c is a key oxidoreductase that mediates the reductive activation of TP053, a thienopyrimidine derivative that kills replicating and non-replicating Mycobacterium tuberculosis. This enzyme transforms nitro-containing compounds to their corresponding amine and uses as a cofactor, a low molecular weight sugar thiol, mycothiol. The Rv2466c structure adopts a thioredoxin-like fold but it forms an unique homodimer in which the C-terminal beta-strand is swapped between the thioredoxin domains of each subunit [1-3]. Rv2466c undergoes significant conformational changes upon formation of its oxidized state [2]. Paper describing PDB structure 4nxi. [1]. 24877756. Rv2466c mediates the activation of TP053 to kill replicating and non-replicating Mycobacterium tuberculosis. Albesa-Jove D, Chiarelli LR, Makarov V, Pasca MR, Urresti S, Mori G, Salina E, Vocat A, Comino N, Mohorko E, Ryabova S, Pfieiffer B, Lopes Ribeiro AL, Rodrigo-Unzueta A, Tersa M, Zanoni G, Buroni S, Altmann KH, Hartkoorn RC, Glockshuber R, Cole ST, Riccardi G, Guerin ME;. ACS Chem Biol. 2014;9:1567-1575. Paper describing PDB structure 4zil. [2]. 26546681. The Redox State Regulates the Conformation of Rv2466c to Activate the Antitubercular Prodrug TP053. Albesa-Jove D, Comino N, Tersa M, Mohorko E, Urresti S, Dainese E, Chiarelli LR, Pasca MR, Manganelli R, Makarov V, Riccardi G, Svergun DI, Glockshuber R, Guerin ME;. J Biol Chem. 2015;290:31077-31089. Paper describing PDB structure 5xur. [3]. 29465985. Identification of a Mycothiol-Dependent Nitroreductase from Mycobacterium tuberculosis. Negri A, Javidnia P, Mu R, Zhang X, V. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-10-16

This family contains a diverse set of proteins with a thioredoxin-like structure Pfam:PF00085. This family also includes 2-hydroxychromene-2-carboxylate (HCCA) isomerase enzymes catalyse one step in prokaryotic polyaromatic hydrocarbon (PAH) catabolic pathways [2,3,4]. This family also contains members with functions other than HCCA isomerisation, such as Kappa family GSTs (e.g. Swiss:P24473), whose similarity to HCCA isomerases was not previously recognised. The sequence Swiss:O07298 has been annotated as a dioxygenase but is almost certainly an HCCA isomerase enzyme. Similarly, the sequence Swiss:Q9ZI67 has been annotated as a dehydrogenase, but is most probably also an HCCA isomerase enzyme. In addition, the Rhizobium leguminosarum Swiss:Q52782 protein has been annotated as a putative glycerol-3-phosphate transfer protein, but is also most likely to be an HCCA isomerase enzyme (see [5]). [1]. 9149147. Structure of TcpG, the DsbA protein folding catalyst from Vibrio cholerae. Hu SH, Peek JA, Rattigan E, Taylor RK, Martin JL;. J Mol Biol 1997;268:137-146. [2]. 8226631. Metabolism of dibenzothiophene and naphthalene in Pseudomonas strains: complete DNA sequence of an upper naphthalene catabolic pathway. Denome SA, Stanley DC, Olson ES, Young KD;. J Bacteriol 1993;175:6890-6901. [3]. 8002605. Organization and evolution of naphthalene catabolic pathways: sequence of the DNA encoding 2-hydroxychromene-2-carboxylate isomerase and trans-o-hydroxybenzylidenepyruvate hydratase-aldolase from the NAH7 plasmid. Eaton RW;. J Bacteriol 1994;176:7757-7762. [4]. 9882667. The phn genes of Burkholderia sp. strain RP007 constitute a dive. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-10-16