Disease relevance of ECs3604

• In addition, we have redefined the substrate specificity of the B. subtilis CysH, formerly designated a PAPS reductase, as an APS reductase, based on its ability to complement a mutant E. coli strain deficient in APS kinase [1].
• In this report, genetic complementation using Escherichia coli mutant strains deficient in APS kinase and PAPS reductase was used to define the M. tuberculosis and Mycobacterium smegmatis CysH enzymes as APS reductases [1].
• The 70% sequence similarity between the Pseudomonas and Escherichia coli APS kinases suggests that the Pseudomonas enzyme may catalyse phosphoryl transfer to the 3'-hydroxyl group of other nucleotides such as dephosphocoenzyme A, as does the purified E. coli APS kinase [2].
• This cross-reactive protein is also present in Pseudomonas strains lacking the gentamicin-resistance plasmid, and apparently reflects an APS kinase analogous to the nodQ-encoded high-molecular-weight APS kinase present in Rhizobium meliloti [2].

High impact information on ECs3604

• The cumulative results indicate that Ser-107 may reside in the substrate binding pocket of fungal APS kinase, but neither it nor any nearby hydroxy amino acid serves as an obligatory phophoryl acceptor in the 3'-phosphoadenylylsulfate synthesis reaction [3].
• Replacement of Ser-107 with alanine yielded an active enzyme with kinetic characteristics similar to those of wild-type APS kinase [3].
• The results also indicate that the absence of a serine at position 478 in the APS kinase-like C-terminal region of fungal ATP sulfurylase does not account for the lack of APS kinase activity in that enzyme [3].
• The sequence includes the structural genes encoding the enzymes ATP sulfurylase (cysD and cysN) and APS kinase (cysC) which catalyze the synthesis of activated sulfate [4].
• APS kinase catalyses the transfer of the gamma phosphoryl group of ATP to the 3'-hydroxyl group of APS [2].

Chemical compound and disease context of ECs3604

• Production of the Pseudomonas aac APS kinase was repressed by cysteine when expressed in E. coli, as is E. coli APS kinase [2].

Biological context of ECs3604

• APS kinase from Escherichia coli is phosphorylated upon incubation with ATP, yielding a protein that can complete the overall reaction through phosphorylation of APS [5].
• In order to elucidate which amino acid residue is phosphorylated, and thus to define the active site region of APS kinase, we have determined the complete sequence of cysC, the structural gene for this enzyme in E. coli [5].

Associations of ECs3604 with chemical compounds

• The enzymes of the sulfate activation pathway, ATP sulfurylase (ATP:sulfate adenylyltransferase, EC 2.7.7.4) and APS kinase (ATP:adenosine-5'-phosphosulfate 3'-phosphotransferase, EC 2.7.1.25) have been overproduced approximately 100-fold [6].
• APS kinase binds one Mn(2+) ion per subunit in the absence of substrates, consistent with the requirement for a divalent cation in the phosphorylation of APS by E-P [7].
• APS kinase requires divalent cations such as Mg(2+) or Mn(2+) for activity [7].

References