PIRSF015617

ATP:cob(I)alamin adenosyltransferase, CobA type

PIRSF entry
Member databasePIRSF
PIRSF typefamily
Short nameAdensltrnsf_CobA

Description

ATP:cob(I)alamin adenosyltransferases () catalyse a step in the biosynthesis of adenosylcobalamin (AdoCbl, coenzyme B12) (either from inactive cobalamins, such as vitamin B12, or via de novo synthesis) and are required for the activity of AdoCbl-dependent enzymes. They transfer an adenosyl moiety from MgATP to a broad range of co(I)rrinoid substrates. ATP:corrinoid adenosyltransferases (ATP:cob(I)alamin adenosyltransferases) are classified into three groups: PduO type (, ), EutT type (), and CobA type (this group, ). The first two groups are very distantly related, sharing short conserved motifs. The third group contains evolutionarily unrelated CobA-type adenosyltransferases
[2]
and is an example of convergent evolution.

Analysis of the genomic context of the genes that encode each of the three groups of ATP:corrinoid adenosyltransferases described above suggests that the three types are specialized for particular AdoCbl-dependent enzymes or for the de novo synthesis of AdoCbl
[1]
. Among members of this group, at least seven proteins are encoded by genes colocalized with genes predicted to function in the de novo synthesis of AdoCbl. Thus, the main role for the CobA-type enzymes is apparently as ATP:corrinoid adenosyltransferases that function in the de novo synthesis of AdoCbl
[1, 6]
. In many organisms, both CobA and PduO-type enzymes are present
[1]
.

CobA belongs to the P-loop-containing family of nucleotide hydrolases. Its overall fold is remarkably similar to that of adenosylcobinamide kinase/adenosylcobinamide guanylyltransferase (CobU in Salmonella typhimurium), RecA protein, and F1ATPase
[4]
. However, these groups share no detectable sequence similarity other than the P-loop
[4]
. It has been speculated that the CobA group originated as a kinase that possessed the normal use of the P-loop
[4]
.

Vitamin B12 (cobalamin) is used as a cofactor in a number of enzyme-catalysed reactions in bacteria, archaea and eukaryotes
[5]
. The biosynthetic pathway to adenosylcobalamin from its five-carbon precursor, 5-aminolevulinic acid, can be divided into three sections: (1) the biosynthesis of uroporphyrinogen III from 5-aminolevulinic acid; (2) the conversion of uroporphyrinogen III into the ring-contracted, deacylated intermediate precorrin-6 or cobalt?precorrin-6; and (3) the transformation of this intermediate to form adenosylcobalamin
[7]
. Cobalamin is synthesized by bacteria and archaea via two alternative routes that differ primarily in the steps of section 2 that lead to the contraction of the macrocycle and excision of the extruded carbon molecule (and its attached methyl group)
[3]
. One pathway (exemplified by Pseudomonas denitrificans) incorporates molecular oxygen into the macrocycle as a prerequisite to ring contraction, and has consequently been termed the aerobic pathway. The alternative, anaerobic, route (exemplified by Salmonella typhimurium) takes advantage of a chelated cobalt ion, in the absence of oxygen, to set the stage for ring contraction
[7]
.

Nomenclature note: CobA, CobO, and BtuR are used as names for members of . In some organisms, CobA may designate unrelated proteins of the cobalamin pathway (e.g., uroporphyrin-III C-methyltransferase, ).

References

1.Functional genomic, biochemical, and genetic characterization of the Salmonella pduO gene, an ATP:cob(I)alamin adenosyltransferase gene. Johnson CL, Pechonick E, Park SD, Havemann GD, Leal NA, Bobik TA. J. Bacteriol. 183, 1577-84, (2001). View articlePMID: 11160088

2.Purification and initial characterization of the ATP:corrinoid adenosyltransferase encoded by the cobA gene of Salmonella typhimurium. Suh S, Escalante-Semerena JC. J. Bacteriol. 177, 921-5, (1995). View articlePMID: 7860601

3.Multiple biosynthetic pathways for vitamin B12: variations on a central theme. Roessner CA, Santander PJ, Scott AI. Vitam. Horm. 61, 267-97, (2001). View articlePMID: 11153269

4.Three-dimensional structure of ATP:corrinoid adenosyltransferase from Salmonella typhimurium in its free state, complexed with MgATP, or complexed with hydroxycobalamin and MgATP. Bauer CB, Fonseca MV, Holden HM, Thoden JB, Thompson TB, Escalante-Semerena JC, Rayment I. Biochemistry 40, 361-74, (2001). View articlePMID: 11148030

5.Salmonella typhimurium cobalamin (vitamin B12) biosynthetic genes: functional studies in S. typhimurium and Escherichia coli. Raux E, Lanois A, Levillayer F, Warren MJ, Brody E, Rambach A, Thermes C. J. Bacteriol. 178, 753-67, (1996). View articlePMID: 8550510

6.The propanediol utilization (pdu) operon of Salmonella enterica serovar Typhimurium LT2 includes genes necessary for formation of polyhedral organelles involved in coenzyme B(12)-dependent 1, 2-propanediol degradation. Bobik TA, Havemann GD, Busch RJ, Williams DS, Aldrich HC. J. Bacteriol. 181, 5967-75, (1999). View articlePMID: 10498708

7.Biosynthesis of cobalamin (vitamin B(12)). Scott AI, Roessner CA. Biochem. Soc. Trans. 30, 613-20, (2002). View articlePMID: 12196148

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