Evolutionary Persistence of the Molybdopyranopterin-Containing Sulfite Oxidase Protein Fold

Abstract

SUMMARY The importance of molybdoenzymes is exemplified both by the debilitating and fatal human diseases caused by their deficiency and by their persistence throughout evolution. Here, we show that the protein fold of the molybdopyranopterin-containing domain of sulfite oxidase (the SUOX fold) can be found in all three domains of life. Analyses of sequence data and protein structure comparisons (secondary structure matching) show that the SUOX fold is found in enzymes that have quite distinct macromolecular architectures comprising one or more domains and sometimes subsidiary subunits. These are summarized as follows: (i) animal SUOXs that contain an N-terminal cytochrome b 5 domain and an SUOX fold fused to a C-terminal dimerization domain; (ii) plant SUOX that contains an SUOX fold fused to a C-terminal dimerization domain; (iii) the YedY protein from Escherichia coli, which comprises only the SUOX fold; (iv) the sulfite dehydrogenase from Starkeya novella that contains the SUOX fold, a dimerization domain, and an additional c-type cytochrome subunit; and (v) the plant-type nitrate reductases, exemplified by that of Pichia angusta, that contain an N-terminal SUOX fold, a dimerization domain, a cytochrome b 5 domain, and a C-terminal NADH binding flavin adenine dinucleotide-containing domain. We used the primary sequences of the proteins containing an SUOX fold to mine 559 sequences of related proteins. A phylogeny of a nonredundant subset of these sequences was generated, and the resultant clades were categorized by sequence motif analyses in the context of the available protein structures. Based on the motif analyses, cladistics, and domain conservations, we are able to postulate a plausible pathway of SUOX fold enzyme evolution.

Analysis of raphidophyte assimilatory nitrate reductase reveals unique domain architecture incorporating a 2/2 hemoglobin

“…NR belongs to the sulfite oxidase fold (SUOX) class of proteins, and sub-arrangements of the domains that comprise NR are analogous to independent extant enzymes, such as sulfite oxidase, cytochrome b5 reductase, and ferredoxin reductase-type enzymes (Workun et al 2008;Karplus and Bruns 1994;Campbell 2001). The domain arrangement of the NR gene is linear with respect to protein function, suggesting that NR evolved by domain shuffling and terminal exon fusion (Workun et al 2008;Campbell 2001).…”

“…The domain arrangement of the NR gene is linear with respect to protein function, suggesting that NR evolved by domain shuffling and terminal exon fusion (Workun et al 2008;Campbell 2001). Although terminal exon fusion is considered to be a major contributor to the formation of novel domain arrangements (Moore et al 2008), a significant number of multi-domain proteins have been identified where a novel domain has been inserted within a preexisting domain (Selvam and Sasidharan 2004).…”

Roles of the twin-arginine translocase and associated chaperones in the biogenesis of the electron transport chains of the human pathogen Campylobacter jejuni

“…Cj0379 is a member of a distinct group of molybdoenzymes (the YedY family) that contain a simple molybdopterin (MPT) cofactor and which are present in a large number of diverse prokaryotes (Workun et al, 2008). Most of the proteins homologous to Cj0379 are encoded in a two-gene operon, designated yedYZ in E. coli.…”

Pyranopterin conformation defines the function of molybdenum and tungsten enzymes

“…These enzymes, known as mononuclear Mo/W enzymes, play pivotal roles in metabolism, global geochemical cycles, and microbial metabolic diversity (2)(3)(4)(5). Their active sites, comprising a Mo or W ion and one or two pyranopterins, catalyze a diversity of redox transformations spanning a reduction potential range of approximately one volt.…”

“…This form is assigned to the xanthine dehydrogenases, and in its cytosine dinucleotide form to the bacterial carbon monoxide dehydrogenases and aldehyde dehydrogenases (these enzymes are referred to collectively as the XDH family). It is also assigned to the sulfite oxidases and plant nitrate reductases [SUOX family (1,5)]. …”