The Physical Biochemistry and Molecular Genetics of Sulfate Activation

Abstract

This article is an overview of current research in the area of sulfate activation. Emphasis is placed on presenting unresolved issues in an appropriate context for critical evaluation by the reader. The energetics of sulfate activation is reevaluated in light of recent findings that demonstrate that the synthesis of activated sulfate is thermodynamically driven by GTP hydrolysis. The structural and functional bases of this GTPase activation are discussed in detail. The bonding and hydrolysis of the high-energy, phosphoric-sulfuric acid anhydride bond of activated sulfate are presented along with an analysis of the importance of the divalent cation and pyrophosphate protonation in the equilibria governing activated sulfate formation. The molecular genetics of sulfate assimilation in prokaryotes is reviewed with an emphasis on the regulation of the pathway. Recent discoveries connecting sulfate activation to plant/microbe symbiogenesis are presented, as are several examples of the importance of activated sulfate in human metabolism and disease.

Structure and Function of Sulfotransferases

“…Earlier kinetic studies showed that cytosolic STs catalyze sequential transfer reactions with the formation of a ternary complex between enzyme, PAPS, and acceptor substrate (30,31). Whether the reaction proceeds through a Bi Bi or ordered mechanism remains controversial.…”

The Xanthomonas oryzae pv.◊oryzae raxP and raxQ genes encode an ATP sulphurylase and adenosine‐5′‐phosphosulphate kinase that are required for AvrXa21 avirulence activity

“…cysJ and cysI encode, respectively, the flavoprotein and haemoprotein of a sulphite reductase (NADPH), whereas cysH encodes a PAPS reductase. Both the cysDNC and the cysJIH operons are required for cysteine synthesis (Leyh, 1993). The similarities to the E. coli genes suggest that the Xoo raxP, raxQ and xcysJ, xcysI and xcysH also encode components of a sulphur assimilation pathway.…”

“…Sulphation requires the presence of the activated sulphate form PAPS, an important intermediate of the sulphate assimilation pathway in all organisms (Leyh, 1993 the adenosine-5¢-phosphoryl moiety of ATP to sulphate to form APS (adenosine-5¢-phosphosulphate). Secondly, APS kinase (ATP:adenylysulphate-3¢-phosphotransferase, EC 2.7.1.25) phosphorylates APS to form PAPS (3¢-phosphoadenosine-5¢-phosphosulphate).…”

“…S. meliloti strains carrying mutations in the nodP, nodQ or nodH genes produce Nod factor that lacks the sulphate group and are severely impaired in their ability to nodulate their normal host alfalfa, but gain the ability to nodulate vetch (Roche et al, 1991). Although it has long been hypothesized that the molecular mechanisms governing the interactions of symbiotic bacteria with their hosts share similarities with phytopathogenic bacteria (Roche et al, 1991), the role of sulphation in controlling the specificity of phytopathogen-host interactions has not yet been demonstrated.Sulphation requires the presence of the activated sulphate form PAPS, an important intermediate of the sulphate assimilation pathway in all organisms (Leyh, 1993 the adenosine-5¢-phosphoryl moiety of ATP to sulphate to form APS (adenosine-5¢-phosphosulphate). Secondly, APS kinase (ATP:adenylysulphate-3¢-phosphotransferase, EC 2.7.1.25) phosphorylates APS to form PAPS (3¢-phosphoadenosine-5¢-phosphosulphate).…”

Identification of sequence polymorphisms in two sulfation-related genes, PAPSS2 and SLC26A2, and an association analysis with knee osteoarthritis

“…Many hormones, neurotransmitters, carbohydrates, and drugs are included in this pathway (Leyh 1993). PAPSS2 and SLC26A2 are expressed ubiquitously in systemic organs (Hastbacka et al 1994;Xu et al 2000).…”