spacer

Overview for MACiE Entry M0140

Version history

General Information

EC Number: 1.17.4.2 (A member of the Oxidoreductases, Acting on CH or CH2 groups, With a disulfide as acceptor)

Enzyme Name: ribonucleoside-triphosphate reductase

Biological Species: Lactobacillus leichmannii (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • Q59490 - Adenosylcobalamin-dependent ribonucleoside-triphosphate reductase

Representative PDB Code: 1l1l - CRYSTAL STRUCTURE OF B-12 DEPENDENT (CLASS II)RIBONUCLEOTIDE REDUCTASE (Resolution = 1.75 Å).

Catalytic CATH Codes:

  • 3.20.70.20 - Anaerobic Ribonucleotide-triphosphate Reductase Large Chain
  • Unassigned Domain

"Other" CATH Codes:

  • 3.90.1390.10 - b-12 dependent (class ii) ribonucleotide reductase, chain A, domain 3
  • 3.30.1620.10 - b-12 dependent (class ii) ribonucleotide reductase, Chain A, Domain 2

Display structure information

Overall Reaction:

Image of thioredoxin

Image of ribonucleoside triphosphate

right arrow

Image of oxidised thioredoxin

Image of water

Image of 2'-deoxyribonucleoside triphosphate

thioredoxin
C00342
CHEBI:15967
ribonucleoside triphosphate
C03802
CHEBI:17972
oxidised thioredoxin
C00343
CHEBI:18191
water
C00001
CHEBI:15377
2'-deoxyribonucleoside triphosphate
C04283
CHEBI:16516

Overall Comment: Catalytic residues Cys731 and Cys736 are not present in the crystal structure reported in PDB code 1l1l, but present in the amino acid sequence crystallised for the experiments.


View similar reactions


Stepwise Description of the Reaction

Step 1The cofactor (a deoxy derivative of vitamin B12) decomposes via a homolysis reaction to produce B12 (the cobalamine, cobalt containing, portion) and deoxyadenosyl (annotated as B12R) portion.
Step 2The deoxyadenosyl radical is transferred to Cys408 via a hydrogen transfer reaction
Step 3The radical on the sulfur of Cys408 is transferred to the ribonucleoside triphosphate substrate via a hydrogen transfer reaction.
Step 4Glu410 deprotonates the ribonucleoside radical, reducing the secondary alcohol group to a ketone group and transfers the radical to the next carbon along, resulting in the elimination of water and concomitant deprotonation of Cys119.
Step 5The deoxyibonucleoside intermediate acquires a hydrogen from Cys419, transferring the radical to this residue. Cys419 then undergoes attack from Cys119, forming a disulfide bond
Step 6The radical on the Cys419-Cys119 species is transferred through a chain of hydrogen bonded active site residues, Asn406 and Glu410, to the substrate 2'-position. The ketone group is then re-oxidised to a secondary alcohol with concomitant deprotonation of Glu410
Step 7The 2'-deoxyribonucleoside triphosphate product is formed by hydrogen transfer from Cys408, generating a thiyl radical
Step 8The thiyl radical of Cys408 is transferred back to the deoxyadenosine via a hydrogen transfer.
Step 9The cofactor is regenerated via a colligation reaction between the cobalamine portion and the deoxyadenosyl portion
Step 10The disulfide bond between Cys119 and Cys419 is transferred to Cys419 and Cys731 with concomitant proton transfer to Cys119. The exact order of events is unclear
Step 11The disulfide bond between Cys419 and Cys731 is transferred to Cys731 and Cys736 with concomitant proton transfer to Cys419. The exact order of events is unclear
Step 12The disulfide bond between Cys731 and Cys736 is transferred to Cys736 and the thioredoxin acceptor with concomitant proton transfer to Cys731. The exact order of events is unclear
Step 13The disulfide bond between Cys736 and thioredoxin is transferred to the second free thiol of thioredoxin with concomitant proton transfer to Cys736, regenerating the enzyme and producing the fully oxidised thioredoxin. The exact order of events is unclear

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Cys 119 A Side Chain
Asn 406 A Side Chain
Cys 408 A Side Chain
Glu 410 A Side Chain
Cys 419 A Side Chain
Cys 731 A Side Chain
Cys 736 A Side Chain

Organic Cofactors for M0140

Type Identity Chain
Vitamin B12 B12 0 Overview

Metal Cofactors for M0140

Type Het group Number Chain
cobalt CO(not in PDB) 1 x Overview

References

  1. M. Kolberg et al. (2004), Biochim. Biophys. Acta, 1699, 1-34. Structure, function, and mechanism of ribonucleotide reductases.
    Medline: 15158709
  2. J. Stubbe et al. (1998), Chem. Rev., 98, 705-762. Protein Radicals in Enzyme Catalysis.
    Medline: 11848913

Homologue information for M0140 (1l1l)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0030 formate C-acetyltransferase
2.3.1.54
2pfl 3.20.70.20
0.33330.3912Compare

Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

GOA logo
nucleotide binding (molecular function)
catalytic activity (molecular function)
ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor (molecular function)
ribonucleoside-diphosphate reductase complex (cellular component)
DNA replication (biological process)
metabolic process (biological process)
ribonucleoside-triphosphate reductase activity (molecular function)
oxidoreductase activity (molecular function)
cobalamin binding (molecular function)
oxidation-reduction process (biological process)
spacer
spacer