PMID- 23627491
OWN - NLM
STAT- MEDLINE
DCOM- 20131210
LR  - 20240318
IS  - 1520-5126 (Electronic)
IS  - 0002-7863 (Print)
IS  - 0002-7863 (Linking)
VI  - 135
IP  - 18
DP  - 2013 May 8
TI  - Identification of a cyclic nucleotide as a cryptic intermediate in molybdenum 
      cofactor biosynthesis.
PG  - 7019-32
LID - 10.1021/ja401781t [doi]
AB  - The molybdenum cofactor (Moco) is a redox cofactor found in all kingdoms of life, 
      and its biosynthesis is essential for survival of many organisms, including 
      humans. The first step of Moco biosynthesis is a unique transformation of 
      guanosine 5'-triphosphate (GTP) into cyclic pyranopterin monophosphate (cPMP). In 
      bacteria, MoaA and MoaC catalyze this transformation, although the specific 
      functions of these enzymes were not fully understood. Here, we report the first 
      isolation and structural characterization of a product of MoaA. This molecule was 
      isolated under anaerobic conditions from a solution of MoaA incubated with GTP, 
      S-adenosyl-L-methionine, and sodium dithionite in the absence of MoaC. Structural 
      characterization by chemical derivatization, MS, and NMR spectroscopy suggested 
      the structure of this molecule to be (8S)-3',8-cyclo-7,8-dihydroguanosine 
      5'-triphosphate (3',8-cH2GTP). The isolated 3',8-cH2GTP was converted to cPMP by 
      MoaC or its human homologue, MOCS1B, with high specificities (Km < 0.060 muM and 
      0.79 +/- 0.24 muM for MoaC and MOCS1B, respectively), suggesting the physiological 
      relevance of 3',8-cH2GTP. These observations, in combination with some 
      mechanistic studies of MoaA, unambiguously demonstrate that MoaA catalyzes a 
      unique radical C-C bond formation reaction and that, in contrast to previous 
      proposals, MoaC plays a major role in the complex rearrangement to generate the 
      pyranopterin ring.
FAU - Hover, Bradley M
AU  - Hover BM
AD  - Department of Biochemistry, Duke University Medical Center, Durham, North 
      Carolina 27710, United States.
FAU - Loksztejn, Anna
AU  - Loksztejn A
FAU - Ribeiro, Anthony A
AU  - Ribeiro AA
FAU - Yokoyama, Kenichi
AU  - Yokoyama K
LA  - eng
GR  - P30 CA014236/CA/NCI NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - P30-CA014236/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130429
PL  - United States
TA  - J Am Chem Soc
JT  - Journal of the American Chemical Society
JID - 7503056
RN  - 0 (Coenzymes)
RN  - 0 (Metalloproteins)
RN  - 0 (Molybdenum Cofactors)
RN  - 0 (Nucleotides, Cyclic)
RN  - 0 (Pteridines)
RN  - ATN6EG42UQ (molybdenum cofactor)
RN  - EC 3.- (Hydrolases)
RN  - EC 3.3.1.2 (S-adenosylmethionine enzyme MoaA, Staphylococcus aureus)
SB  - IM
MH  - Biocatalysis
MH  - Coenzymes/chemistry/*metabolism
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Hydrolases/metabolism
MH  - Metalloproteins/chemistry/*metabolism
MH  - Models, Molecular
MH  - Molecular Conformation
MH  - Molybdenum Cofactors
MH  - Nucleotides, Cyclic/*biosynthesis/chemistry
MH  - Pteridines/chemistry/*metabolism
PMC - PMC3777439
MID - NIHMS474396
EDAT- 2013/05/01 06:00
MHDA- 2013/12/16 06:00
PMCR- 2014/05/08
CRDT- 2013/05/01 06:00
PHST- 2013/05/01 06:00 [entrez]
PHST- 2013/05/01 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2014/05/08 00:00 [pmc-release]
AID - 10.1021/ja401781t [doi]
PST - ppublish
SO  - J Am Chem Soc. 2013 May 8;135(18):7019-32. doi: 10.1021/ja401781t. Epub 2013 Apr 
      29.