The Last Piece in the Vitamin B1 Biosynthesis Puzzle

Coquille, S.C.; Roux, Cécile; Fitzpatrick, Thérésa Bridget; Thore, Stéphane

doi:10.1074/jbc.m112.397240

Cited by 28 publications

(12 citation statements)

References 38 publications

(9 reference statements)

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“…The finding that SNZ2 and/or SNZ3 are important for thiamine, specifically HMP, synthesis supports a connection between SNZ2/3 and the Thi5p family of enzymes. The poorly characterized Thi5p enzymes use PLP as a substrate rather than a co-factor to generate the HMP-P moiety used for thiamine synthesis (Lai et al 2012; Coquille et al 2012). The finding that the lack of a specific SNZ paralog impacts thiamine biosynthesis, out of many metabolic pathways that use PLP as a cofactor, suggests that there are unique requirements for PLP in this pathway, likely involving the Thi5p family of enzymes.…”

Section: Resultsmentioning

confidence: 99%

SNZ3 Encodes a PLP Synthase Involved in Thiamine Synthesis in Saccharomyces cerevisiae

Paxhia

Downs

2019

G3 Genes|Genomes|Genetics

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Pyridoxal 5′-phosphate (the active form of vitamin B 6 ) is a cofactor that is important for a broad number of biochemical reactions and is essential for all forms of life. Organisms that can synthesize pyridoxal 5′-phosphate use either the deoxyxylulose phosphate-dependent or -independent pathway, the latter is encoded by a two-component pyridoxal 5′-phosphate synthase. Saccharomyces cerevisiae contains three paralogs of the two-component SNZ/SNO pyridoxal 5′-phosphate synthase. Past work identified the biochemical activity of Snz1p , Sno1p and provided in vivo data that SNZ1 was involved in pyridoxal 5′-phosphate biosynthesis. Snz2p and Snz3p were considered redundant isozymes and no growth condition requiring their activity was reported. Genetic data herein showed that either SNZ2 or SNZ3 are required for efficient thiamine biosynthesis in Saccharomyces cerevisiae . Further, SNZ2 or SNZ3 alone could satisfy the cellular requirement for pyridoxal 5′-phosphate (and thiamine), while SNZ1 was sufficient for pyridoxal 5′-phosphate synthesis only if thiamine was provided. qRT-PCR analysis determined that SNZ2 , 3 are repressed ten-fold by the presence thiamine. In total, the data were consistent with a requirement for PLP in thiamine synthesis, perhaps in the Thi5p enzyme, that could only be satisfied by SNZ2 or SNZ3 . Additional data showed that Snz3p is a pyridoxal 5′-phosphate synthase in vitro and is sufficient to satisfy the pyridoxal 5′-phosphate requirement in Salmonella enterica when the medium has excess ammonia.

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Section: Resultsmentioning

confidence: 99%

SNZ3 Encodes a PLP Synthase Involved in Thiamine Synthesis in Saccharomyces cerevisiae

Paxhia

Downs

2019

G3 Genes|Genomes|Genetics

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“…The process of thiazole heterocycle formation is relatively well understood both chemically and structurally in prokaryotes and eukaryotes (Chatterjee et al, 2006, 2007; Jurgenson et al, 2006; Kriek et al, 2007). The formation of the pyrimidine moiety, 4-ami-no-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P), is catalyzed by the THIC enzyme in bacteria and in plants or by the THI5 proteins in yeast (Wightman and Meacock, 2003; Lawhorn et al, 2004; Raschke et al, 2007; Ishida et al 2008; Lai et al, 2012; Coquille et al, 2012). Isotopic labeling and reconstitution studies have shown that THIC uses 5-amino-imidazole ribonucleotide (AIR) as a substrate (Zeidler et al, 2003; Lawhorn et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

High-resolution crystal structure of the eukaryotic HMP-P synthase (THIC) from Arabidopsis thaliana

Coquille

Roux

Mehta

et al. 2013

Journal of Structural Biology

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Vitamin B1 is an essential compound in all organisms acting as a cofactor in key metabolic reactions. It is formed by the condensation of two independently biosynthesized molecules referred to as the pyrimidine and thiazole moieties. In bacteria and plants, the biosynthesis of the pyrimidine moiety, 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P), requires a single enzyme, THIC (HMP-P synthase). The enzyme uses an iron–sulfur cluster as well as a 5’-deoxyadenosyl radical as cofactors to rearrange the 5-amino-imidazole ribonucleotide (AIR) substrate to the pyrimidine ring. So far, the only structure reported is the one from the bacteria Caulobacter crescentus. In an attempt to structurally characterize an eukaryotic HMP-P synthase, we have determined the high-resolution crystal structure of THIC from Arabidopsis thaliana at 1.6 Å. The structure is highly similar to its bacterial counterpart although several loop regions show significant differences with potential implications for the enzymatic properties. Furthermore, we have found a metal ion with octahedral coordination at the same location as a zinc ion in the bacterial enzyme. Our high-resolution atomic model shows a metal ion with multiple coordinated water molecules in the close vicinity of the substrate binding sites and is an important step toward the full characterization of the chemical rearrangement occurring during HMP-P biosynthesis.

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“…Opening of the Sc MqnA active site can be seen as a combined result of local conformational changes—especially of the 109 to 112 region—and a slight rotation of the two lobes. Interestingly, other VFT enzymes, such as desulfinase DszB ( 26 ), thiaminase I, and thiamin pyrimidine synthase Thi5 ( 27 , 28 ), also show local rearrangements of loops and α-helices at the opening of the active site, with negligible motion of the two lobes toward each other. Taken together, these observations suggest that enzymes exploit the ligand-binding properties of the VFT fold for specific substrate binding and catalysis but restrict conformational changes largely to the immediate proximity of the active site.…”

Section: Resultsmentioning

confidence: 99%

Mechanism of chorismate dehydratase MqnA, the first enzyme of the futalosine pathway, proceeds via substrate-assisted catalysis

Prasad¹,

Breithaupt²,

Nguyen³

et al. 2022

Journal of Biological Chemistry

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The Last Piece in the Vitamin B1 Biosynthesis Puzzle

Cited by 28 publications

References 38 publications

SNZ3 Encodes a PLP Synthase Involved in Thiamine Synthesis in Saccharomyces cerevisiae

SNZ3 Encodes a PLP Synthase Involved in Thiamine Synthesis in Saccharomyces cerevisiae

High-resolution crystal structure of the eukaryotic HMP-P synthase (THIC) from Arabidopsis thaliana

Mechanism of chorismate dehydratase MqnA, the first enzyme of the futalosine pathway, proceeds via substrate-assisted catalysis

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