Adenylyl-sulfate reductase (EC1.8.99.2) is an enzyme that catalyzes the chemical reaction of the reduction of adenylyl-sulfate/adenosine-5'-phosphosulfate (APS) to sulfite through the use of an electron donor cofactor. The products of the reaction are AMP and sulfite, as well as an oxidized electron donor cofactor.
This enzyme belongs to the family of oxidoreductases, specifically those acting on a sulfur group of donors with other acceptors. The systematic name of this enzyme class is AMP, sulfite:acceptor oxidoreductase (adenosine-5'-phosphosulfate-forming). Other names in common use include adenosine phosphosulfate reductase, adenosine 5'-phosphosulfate reductase, APS-reductase, APS reductase, AMP, sulfite:(acceptor) oxidoreductase, and (adenosine-5'-phosphosulfate-forming). This enzyme participates in selenium metabolism and sulfur metabolism.[1]
Mechanism
APS reductase catalyzes the reversible transformation of APS to sulfite and AMP, which is the rate determining step of the overall reaction.[2] The reaction catalyzed by APS reductase is as follows:
Sulfate has to be activated to APS by ATP sulfurylase at the expense of one ATP, hence this reaction requires an input of energy.[2] The reaction above occurs in a strictly anaerobic environment.[2] The two electrons come from a reduced cofactor, in this case reduced FAD.[3] The forward direction requires one AMP molecule; however, research suggests that the reverse reaction requires two AMP molecules (one acting on the substrate and one inhibiting the forward reaction).[3] The reversible reaction occurs when AMP binds to the Arg317 residue, changing the confirmation of Arg317 and APS reductase as a whole, which provides the thermodynamic driving force to go in the reverse direction.[3]
APS reductases are involved in both assimilatory and dissimilatory sulfate reduction.[4] Dissimilatory sulfate reduction takes sulfate and transforms it into sulfide, a sulfur source that can be distributed throughout the body.[4] Assimilatory sulfate reduction takes sulfate and turns it into cysteine.[4] Dissimilatory and assimilatory pathways both use APS reductases as a metabolic tool to produce a sulfur source and amino acids, respectively.[4]
The reduction of activated sulfur in the form of adenosine-5'-phosphosulfate to sulfite, catalyzed by adenosine-5'-phosphosulfate reductase with thioredoxin as the reducing agent.
The monomer of the enzyme consists of a mix of α-helices and β-sheets (both parallel and antiparallel). The protein cofactor thioredoxin can provide the required reducing equivalents for the reaction in the form of two cysteine residues, which are ultimately oxidized to a disulfide bond.[5] The base active form of APS reductase appears to be a heterodimer, as seen in plants.[6] In both bacteria and plants, two heterodimers tend to form together and produce a heterotetramer.[7]
The active site cleft in bacterial APS reductase has a few key elements. Residue sequences that appear to be necessary for catalysis are the P-loop (residues 60-66), the Arg-loop (residues 162-173), and the LDTG motif (residues 85-88). The P-loop, or phosphate-binding loop, is an especially important consecutive sequence of resides which aids in the recognition of the phosphate group in APS and, as a result, influences the substrate specificity for APS reductase. The C-terminal Cys256 is also catalytically essential, and seems to have a role in changing the conformation of the enzyme during catalysis.[5]
One notable chemical motif that distinguishes APS reductase from the related 3'-phosphoadenosine-5'-phosphosulfate (PAPS) reductase is the presence of a conserved cysteine motif, CC-X~80-CXXC, which occurs in addition to the universally conserved catalytic cysteine residue. This motif is correlated with the presence of a [4Fe-4S] cluster; therefore, these iron-sulfur clusters are not present within PAPS reductase. When the iron-sulfur cluster is present, it is required for catalytic activity and coordinated to the four cysteine residues in the conserved motif on the other side of the active site cleft.[5]
Function
Sulfur is a vital component in biological life and a key element in amino acids cysteine and methionine.[6] APS reductase controls the rate limiting step of endogenous sulfur assimilation, which is the process of producing hydrogen sulfide from sulfite. Hydrogen sulfite is one of the major sources of sulfur in plants.[6] APS reductase controls the flow of inorganic sulfur to cysteine, which is involved in many biological processes in plants such as growth, development, and responses to biotic and abiotic stresses.[6] In fact, studies have shown that when cells are starved of sulfur, APS reductase gene expression fluctuates, indicating that when the plants are exposed to metabolic and regulatory stress, APS reductase is likely a crucial enzyme in producing hydrogen sulfide and restoring homeostasis.[6]
Bacteria use APS reductases to engage in assimilatory and dissimilatory sulfate reduction, which make them prime candidates to appear in wastewater treatment environments.[8] Biofoulants can contain a number of sulfate reducing bacteria, and studies have shown that if wastewater plants are left untreated sulfate levels will decrease.[8] These studies have further solidified APS reductase’s crucial role in the global sulfur cycle by giving organisms another unique way to obtain sulfur when it's unavailable.[8]
Clinical significance
APS reductase does not exist within the proteome of human cells; consequently, these enzymes have become the targets of research for various environmental and medical reasons. Competitive inhibitors for the APS reductase in Mycobacterium tuberculosis have been studied as a new possible route for TB treatment, especially against drug-resistant and latent TB.[9] Such inhibitors have also been studied in the context of obtaining oil and gas from reservoirs in order to better control the souring of such products.[10]
Some APS reductases have also been investigated for their role in selenium metabolism and reduction due to the chemical similarity between sulfur and selenium. APR2, the dominant APS reductase isozyme in the model plant Arabidopsis thaliana, has been implicated in the involvement of selenate tolerance and selenite metabolism. Such research may then aid in the goal of enhancing selenium phytoremediation in plants and, as a result, dietary biofortification.[1]
Related Research Articles
Sulfate-reducing microorganisms (SRM) or sulfate-reducing prokaryotes (SRP) are a group composed of sulfate-reducing bacteria (SRB) and sulfate-reducing archaea (SRA), both of which can perform anaerobic respiration utilizing sulfate (SO2− 4) as terminal electron acceptor, reducing it to hydrogen sulfide (H2S). Therefore, these sulfidogenic microorganisms "breathe" sulfate rather than molecular oxygen (O2), which is the terminal electron acceptor reduced to water (H2O) in aerobic respiration.
Sulfonucleotide reductases are a class of enzymes involved in reductive sulfur assimilation. This reaction consists of a conversion from activated sulfate to sulfite.. The sulfite is used in essential biomolecules such as cysteine. The sulfonucleotide reductases are through to have all evolved from a common ancestor.
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3′-Phosphoadenosine-5′-phosphosulfate (PAPS) is a derivative of adenosine monophosphate (AMP) that is phosphorylated at the 3′ position and has a sulfate group attached to the 5′ phosphate. It is the most common coenzyme in sulfotransferase reactions and hence part of sulfation pathways. It is endogenously synthesized by organisms via the phosphorylation of adenosine 5′-phosphosulfate (APS), an intermediary metabolite. In humans such reaction is performed by bifunctional 3′-phosphoadenosine 5′-phosphosulfate synthases using ATP as the phosphate donor.
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Adenylyl-sulfate reductase (glutathione) is an enzyme that catalyzes the chemical reaction
Adenylyl-sulfate reductase (thioredoxin) is an enzyme that catalyzes the chemical reaction
In enzymology, a phosphoadenylyl-sulfate reductase (thioredoxin) is an enzyme that catalyzes the chemical reaction
Sulfite reductases (EC 1.8.99.1) are enzymes that participate in sulfur metabolism. They catalyze the reduction of sulfite to hydrogen sulfide and water. Electrons for the reaction are provided by a dissociable molecule of either NADPH, bound flavins, or ferredoxins.
The enzyme cysteine lyase catalyzes the chemical reaction
In enzymology, a thiol sulfotransferase is an enzyme that catalyzes the chemical reaction
In enzymology, an adenylylsulfatase is an enzyme that catalyzes the chemical reaction
In enzymology, an adenylyl-sulfate kinase is an enzyme that catalyzes the chemical reaction
In enzymology, a sulfate adenylyltransferase is an enzyme that catalyzes the chemical reaction
Sulfur is metabolized by all organisms, from bacteria and archaea to plants and animals. Sulfur can have an oxidation state from -2 to +6 and is reduced or oxidized by a diverse range of organisms. The element is present in proteins, sulfate esters of polysaccharides, steroids, phenols, and sulfur-containing coenzymes.
Siroheme is a heme-like prosthetic group at the active sites of some enzymes to accomplish the six-electron reduction of sulfur and nitrogen. It is a cofactor at the active site of sulfite reductase, which plays a major role in sulfur assimilation pathway, converting sulfite into sulfide, which can be incorporated into the organic compound homocysteine.
Dissimilatory sulfate reduction is a form of anaerobic respiration that uses sulfate as the terminal electron acceptor to produce hydrogen sulfide. This metabolism is found in some types of bacteria and archaea which are often termed sulfate-reducing organisms. The term "dissimilatory" is used when hydrogen sulfide is produced in an anaerobic respiration process. By contrast, the term "assimilatory" would be used in relation to the biosynthesis of organosulfur compounds, even though hydrogen sulfide may be an intermediate.
Dissimilatory sulfite reductase is an enzyme that participates in sulfur metabolism in dissimilatory sulfate reduction.
Prosthecochloris aestuarii is a green sulfur bacterium in the genus Prosthecochloris. This organism was originally isolated from brackish lagoons located in Sasyk-Sivash and Sivash. They are characterized by the presence of "prosthecae" on their cell surface; the inner part of these appendages house the photosynthetic machinery within chlorosomes, which are characteristic structures of green sulfur bacteria. Additionally, like other green sulfur bacteria, they are Gram-negative, non-motile, and non-spore forming. Of the four major groups of green sulfur bacteria, P. aestuarii serves as the type species for Group 4.
References
1 2 Grant K, Carey NM, Mendoza M, Schulze J, Pilon M, Pilon-Smits EA, van Hoewyk D (September 2011). "Adenosine 5'-phosphosulfate reductase (APR2) mutation in Arabidopsis implicates glutathione deficiency in selenate toxicity". The Biochemical Journal. 438 (2): 325–35. doi:10.1042/BJ20110025. PMID21585336.
1 2 3 4 Schiffer A, Fritz G, Kroneck PM, Ermler U (March 2006). "Reaction mechanism of the iron-sulfur flavoenzyme adenosine-5'-phosphosulfate reductase based on the structural characterization of different enzymatic states". Biochemistry. 45 (9): 2960–7. doi:10.1021/bi0521689. PMID16503650.
1 2 3 Zhou L, Ou P, Zhao B, Zhang W, Yu K, Xie K, Zhuang WQ (January 2021). "Assimilatory and dissimilatory sulfate reduction in the bacterial diversity of biofoulant from a full-scale biofilm-membrane bioreactor for textile wastewater treatment". The Science of the Total Environment. 772: 145464. Bibcode:2021ScTEn.77245464Z. doi:10.1016/j.scitotenv.2021.145464. PMID33571768. S2CID231898490.
↑ Dos Santos ES, de Souza LC, de Assis PN, Almeida PF, Ramos-de-Souza E (2014). "Novel potential inhibitors for adenylylsulfate reductase to control souring of water in oil industries". Journal of Biomolecular Structure & Dynamics. 32 (11): 1780–92. doi:10.1080/07391102.2013.834850. PMID24028628. S2CID31496404.
Further reading
Michaels GB, Davidson JT, Peck HD (May 1970). "A flavin-sulfite adduct as an intermediate in the reaction catalyzed by adenylyl sulfate reductase from Desulfovibrio vulgaris". Biochemical and Biophysical Research Communications. 39 (3): 321–8. doi:10.1016/0006-291X(70)90579-6. PMID5421934.
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