KEGG   ENZYME: 1.17.4.2Help
Entry
EC 1.17.4.2                 Enzyme                                 

Name
ribonucleoside-triphosphate reductase (thioredoxin);
ribonucleotide reductase (ambiguous);
2'-deoxyribonucleoside-triphosphate:oxidized-thioredoxin 2'-oxidoreductase
Class
Oxidoreductases;
Acting on CH or CH2 groups;
With a disulfide as acceptor
BRITE hierarchy
Sysname
2'-deoxyribonucleoside-5'-triphosphate:thioredoxin-disulfide 2'-oxidoreductase
Reaction(IUBMB)
2'-deoxyribonucleoside 5'-triphosphate + thioredoxin disulfide + H2O = ribonucleoside 5'-triphosphate + thioredoxin [RN:R04315]
Reaction(KEGG)
Substrate
2'-deoxyribonucleoside 5'-triphosphate [CPD:C00677];
thioredoxin disulfide [CPD:C00343];
H2O [CPD:C00001]
Product
ribonucleoside 5'-triphosphate [CPD:C03802];
thioredoxin [CPD:C00342]
Comment
The enzyme, characterized from the bacterium Lactobacillus leichmannii, is similar to class II ribonucleoside-diphosphate reductase (cf. EC 1.17.4.1). However, it is specific for the triphosphate versions of its substrates. The enzyme contains an adenosylcobalamin cofactor that is involved in generation of a transient thiyl (sulfanyl) radical on a cysteine residue. This radical attacks the substrate, forming a ribonucleotide 3'-radical, followed by water loss to form a ketyl (alpha-oxoalkyl) radical. The ketyl radical is reduced to 3'-keto-deoxynucleotide concomitant with formation of a disulfide anion radical between two cysteine residues. A proton-coupled electron-transfer from the disulfide radical to the substrate generates a 3'-deoxynucleotide radical, and the final product is formed when the hydrogen atom that was initially removed from the 3'-position of the nucleotide by the thiyl radical is returned to the same position. The disulfide bridge is reduced by the action of thioredoxin. cf. EC 1.1.98.6, ribonucleoside-triphosphate reductase (formate).
History
EC 1.17.4.2 created 1972, modified 2017
Pathway
ec00230  Purine metabolism
ec00240  Pyrimidine metabolism
ec01100  Metabolic pathways
Orthology
K00527  ribonucleoside-triphosphate reductase (thioredoxin)
Genes
BSED: DN745_16470
PPQ: PPSQR21_032590
LAC: LBA0041
LAI: LAC30SC_00160
LAD: LA14_0040
LAF: SD55_0041(nrdJ)
LDB: Ldb0096(rtpR)
LBU: LBUL_0079
LDE: LDBND_0069(rtpR)
LDL: LBU_0061
LBR: LVIS_1898
LCA: LSEI_2287
LPAP: LBPC_2218
LCB: LCABL_24690(rtpR)
LCS: LCBD_2467
LCE: LC2W_2450
LCW: BN194_24230(rtpR)
LGA: LGAS_1503
LRU: HMPREF0538_20868(nrdJ)
LHE: lhv_0042
LHL: LBHH_0061
LHV: lhe_0057(rtpR)
LHH: LBH_0034
LHD: HUO_01190
LRH: LGG_02296(rtpR)
LRG: LRHM_2207
LRL: LC705_02286(rtpR)
LRA: LRHK_2294(nrdJ)
LAM: LA2_00225
LBH: Lbuc_2266
LBN: LBUCD034_2364(rtpR)
LKE: WANG_1429
LAE: LBAT_0056
SALJ: SMD11_1224
AEY: CDG81_09715(nrdJ)
FLM: MY04_3968
 » show all
Taxonomy
Reference
1  [PMID:14299643]
  Authors
BLAKLEY RL.
  Title
COBAMIDES AND RIBONUCLEOTIDE REDUCTION. I. COBAMIDE STIMULATION OF RIBONUCLEOTIDE REDUCTION IN EXTRACTS OF LACTOBACILLUS LEICHMANNII.
  Journal
J Biol Chem 240:2173-80 (1965)
Reference
2  [PMID:5924645]
  Authors
Goulian M, Beck WS.
  Title
Purification and properties of cobamide-dependent ribonucleotide reductase from Lactobacillus leichmannii.
  Journal
J Biol Chem 241:4233-42 (1966)
Reference
3  [PMID:7014560]
  Authors
Stubbe J, Ackles D, Segal R, Blakley RL
  Title
On the mechanism of ribonucleoside triphosphate reductase from Lactobacillus leichmannii. Evidence for 3' C--H bond cleavage.
  Journal
J Biol Chem 256:4843-6 (1981)
Reference
4  [PMID:3512563]
  Authors
Ashley GW, Harris G, Stubbe J
  Title
The mechanism of Lactobacillus leichmannii ribonucleotide reductase. Evidence for 3' carbon-hydrogen bond cleavage and a unique role for coenzyme B12.
  Journal
J Biol Chem 261:3958-64 (1986)
Reference
5  [PMID:9818192]
  Authors
Lawrence CC, Stubbe J
  Title
The function of adenosylcobalamin in the mechanism of ribonucleoside triphosphate reductase from Lactobacillus leichmannii.
  Journal
Curr Opin Chem Biol 2:650-5 (1998)
DOI:10.1016/S1367-5931(98)80097-5
Reference
6  [PMID:9930982]
  Authors
Licht SS, Booker S, Stubbe J
  Title
Studies on the catalysis of carbon-cobalt bond homolysis by ribonucleoside triphosphate reductase: evidence for concerted carbon-cobalt bond homolysis and thiyl radical formation.
  Journal
Biochemistry 38:1221-33 (1999)
DOI:10.1021/bi981885i
Other DBs
ExplorEnz - The Enzyme Database: 1.17.4.2
IUBMB Enzyme Nomenclature: 1.17.4.2
ExPASy - ENZYME nomenclature database: 1.17.4.2
BRENDA, the Enzyme Database: 1.17.4.2
CAS: 9068-66-0

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