Reaction: (1) a [4Fe-5S] iron-sulfur cluster linked by 3 L-cysteine residues + pyridin-1-ium-3,5-dicarboxylate mononucleotide + ATP + reduced acceptor = a [4Fe-4S] iron-sulfur cluster linked by 3 L-cysteine residues + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide + AMP + diphosphate + acceptor (overall reaction)
(1a) ATP + pyridin-1-ium-3,5-dicarboxylate mononucleotide = diphosphate + 5-carboxy-1-(5-O-phospho-β-D-ribofuranosyl)pyridin-1-ium-3-carbonyl adenylate
(1b) a [4Fe-5S] iron-sulfur cluster linked by 3 L-cysteine residues + 5-carboxy-1-(5-O-phospho-β-D-ribofuranosyl)pyridin-1-ium-3-carbonyl adenylate + reduced acceptor = a [4Fe-4S] iron-sulfur cluster linked by 3 L-cysteine residues + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide + AMP + acceptor
(2) a [4Fe-5S] iron-sulfur cluster linked by 3 L-cysteine residues + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide + ATP + reduced acceptor = a [4Fe-4S] iron-sulfur cluster linked by 3 L-cysteine residues + pyridin-1-ium-3,5-bisthiocarboxylate mononucleotide + AMP + diphosphate + acceptor (overall reaction)
(2a) ATP + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide = diphosphate + 1-(5-O-phospho-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl adenylate
(2b) a [4Fe-5S] iron-sulfur cluster linked by 3 L-cysteine residues + 1-(5-O-phospho-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl adenylate + reduced acceptor = a [4Fe-4S] iron-sulfur cluster linked by 3 L-cysteine residues + pyridin-1-ium-3,5-bisthiocarboxylate mononucleotide + AMP + acceptor
Other name(s): larE (gene name)
Systematic name: pyridin-1-ium-3,5-bisthiocarboxylate mononucleotide sufo-lyase
Comments: This enzyme, found in the bacterium Thermotoga maritima, catalyses two complex reactions during the biosynthesis of a nickel-pincer cofactor. The process starts with the adenylation of pyridin-1-ium-3,5-dicarboxylate mononucleotide (P2CMN), which is covalently bound to an intrinsic cysteine residue. Next, a [4Fe-4S] iron-sulfur cluster receives a sulfane sulfur from free L-cysteine via the action of EC 2.8.1.7, cysteine desulfurase, forming a temporary [4Fe-5S] cluster. The sulfur atom then attacks the activated substrate, resulting in formation of pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide (PCTMN). The process repeats twice, with pyridin-1-ium-3,5-bisthiocarboxylate mononucleotide (P2TMN) being the final product. cf. EC 4.4.1.37, intrinsic cysteine-dependent pyridinium-3,5-bisthiocarboxylic acid mononucleotide synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Chatterjee, S., Parson, K.F., Ruotolo, B.T., McCracken, J., Hu, J. and Hausinger, R.P. Characterization of a [4Fe-4S]-dependent LarE sulfur insertase that facilitates nickel-pincer nucleotide cofactor biosynthesis in Thermotoga maritima. J. Biol. Chem. 298 (2022) 102131. [PMID: 35700827]
2. Zecchin, P., Pecqueur, L., Oltmanns, J., Velours, C., Schunemann, V., Fontecave, M. and Golinelli-Pimpaneau, B. Structure-based insights into the mechanism of [4Fe-4S]-dependent sulfur insertase LarE. Protein Sci. 33 (2024) e4874. [PMID: 38100250]