2.0 2012-05-31 14:52:51 -0600 2015-06-03 17:20:22 -0600 ECMDB20601 M2MDB001401 Cyclic pyranopterin monophosphate Cyclic pyranopterin monophosphate is a member of the chemical class known as Pterins and Derivatives. These are polycyclic aromatic compounds containing a pterin moeity, which consist of a pteridine ring bearing a ketone and an amine group to form 2-aminopteridin-4(3H)-one. cPMP is a precursor to molybdenum cofactor, which is required for the enyzme activity of sulfite oxidase, xanthine dehydrogenase/oxidase and aldehyde oxidase. The transition element molybdenum (Mo) has been long known as an essential micronutrient across the kingdoms of plants, animals, fungi and bacteria. However, molybdate itself is catalytically inactive and, with the exception of bacterial nitrogenase, needs to be activated through complexation by a special cofactor. There are several molybdenum cofactors, including molybdopterin (MPT), guanylyl molybdenum cofactor (MGD), cytidylyl molybdenum cofactor, or others. In Escherichia coli, the MoaD protein plays a central role in the conversion of precursor Z to molybdopterin (MPT) during molybdenum cofactor biosynthesis. (PMID 17223713) In Escherichia coli, MPT is formed by incorporation of two sulfur atoms into precursor Z, which is catalyzed by MPT synthase. (PMID 11459846) 8-Amino-2,12,12-trihydroxy-4,4a,5a,6,9,10,11,11a,12,12a-decahydro-[1,3,2]dioxaphosphinino[4',5':5,6]pyrano[3,2-g]pteridine 2-oxide 8-Amino-2,12,12-trihydroxy-4a,5a,6,9,11,11a,12,12a-octahydro[1,3,2]dioxaphosphinino[4',5':5,6]pyrano[3,2-g]pteridin-10(4H)-one 2-oxide CPMP Cyclic pyranopterin monophosphate Cyclic pyranopterin monophosphoric acid Precursor z Precursor-Z C10H14N5O8P 363.2206 363.057998961 (4aR,5aR,11aR,12aS)-2,10,12,12-tetrahydroxy-8-imino-4,4a,5a,6,7,8,11,11a,12,12a-decahydro-2H-1,3,5-trioxa-6,7,9,11-tetraaza-2lambda5-phosphatetracen-2-one (4aR,5aR,11aR,12aS)-2,10,12,12-tetrahydroxy-8-imino-4,4a,5a,6,7,11,11a,12a-octahydro-1,3,5-trioxa-6,7,9,11-tetraaza-2lambda5-phosphatetracen-2-one [H][C@@]12COP(O)(=O)O[C@]1([H])C(O)(O)[C@]1([H])NC3=C(NC(=N)N=C3O)N[C@]1([H])O2 InChI=1S/C10H14N5O8P/c11-9-14-6-3(7(16)15-9)12-4-8(13-6)22-2-1-21-24(19,20)23-5(2)10(4,17)18/h2,4-5,8,12,17-18H,1H2,(H,19,20)(H4,11,13,14,15,16)/t2-,4-,5+,8-/m1/s1 CZAKJJUNKNPTTO-AJFJRRQVSA-N Cytosol logp -1.97 ALOGPS logs -1.60 ALOGPS solubility 9.05e+00 g/l ALOGPS logp -3.2 ChemAxon pka_strongest_acidic 1.8 ChemAxon pka_strongest_basic 3.96 ChemAxon iupac (4aR,5aR,11aR,12aS)-2,10,12,12-tetrahydroxy-8-imino-4,4a,5a,6,7,8,11,11a,12,12a-decahydro-2H-1,3,5-trioxa-6,7,9,11-tetraaza-2lambda5-phosphatetracen-2-one ChemAxon average_mass 363.2206 ChemAxon mono_mass 363.057998961 ChemAxon smiles [H][C@@]12COP(O)(=O)O[C@]1([H])C(O)(O)[C@]1([H])NC3=C(NC(=N)N=C3O)N[C@]1([H])O2 ChemAxon formula C10H14N5O8P ChemAxon inchi InChI=1S/C10H14N5O8P/c11-9-14-6-3(7(16)15-9)12-4-8(13-6)22-2-1-21-24(19,20)23-5(2)10(4,17)18/h2,4-5,8,12,17-18H,1H2,(H,19,20)(H4,11,13,14,15,16)/t2-,4-,5+,8-/m1/s1 ChemAxon inchikey CZAKJJUNKNPTTO-AJFJRRQVSA-N ChemAxon polar_surface_area 197.98 ChemAxon refractivity 93.04 ChemAxon polarizability 29.91 ChemAxon rotatable_bond_count 0 ChemAxon acceptor_count 11 ChemAxon donor_count 8 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Folate biosynthesis The biosynthesis of folic acid begins with a product of purine nucleotides de novo biosynthesis pathway, GTP. This compound is involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphatased through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter compound reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. This compound reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. The latter compound is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate. Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter compound then reacts through an aminodeoxychorismate lyase resulting in pyruvic acid,hydrogen ion and p-aminobenzoic acid. (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react through a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthetase / dihydrofolate synthetase resulting in a 7,8-dihydrofolate monoglutamate. This compound is reduced through an NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate. This product goes on to a one carbon pool by folate pathway. PW000908 ec00790 Metabolic Metabolic pathways eco01100 GTP degradation GTP, produced in the nucleotide de novo biosyntheis pathway, interacts with a water molecule through a GTP cyclohydrolase resulting in a formate, hydrogen ion and a 7,8-dihydroneopterin 3'-triphosphate. The latter compound interacts with a water molecule through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, a hydrogen ion and a 7,8-dihydroneopterin 3'-phosphate. The latter compound interacts with water spontaneously resulting in the release of a phosphate and a 7,8 dihydroneopterin. The latter compound interacts with a dihydroneopterin aldolase resulting in the release of a glycolaldehyde and a 6-hydroxymethyl-7,8-dihydropterin. This compound then is then diphosphorylated by reacting with a ATP driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in the release of a hydrogen ion, an AMP and 6-hydroxymethyl-7,8-dihydropterin diphosphate. GTP interacts with a cyclic pyranopterin monophosphate synthase resulting in the release of a diphosphate and a cyclic pyranopterin phosphate. The latter compound interacts with a thiocarboxylated small subunit of molybdopterin synthase (a protein) and a water molecule through a molybdopterin synthase resulting in the release of 4 hydrogen ions, 2 small subunits of molybdopterin synthase and a molybdopterin. The molybdopterin interacts with an ATP and a hydrogen ion through a molybdopterin adenylyltransferase resulting in the release of a diphosphate and a molybdopterin adenine dinucleotide. PW001888 Metabolic molybdenum cofactor biosynthesis PWY-6823 Specdb::CMs 34723 Specdb::CMs 47831 Specdb::CMs 133650 Specdb::CMs 141384 Specdb::NmrOneD 51742 Specdb::NmrOneD 51743 Specdb::NmrOneD 51744 Specdb::NmrOneD 51745 Specdb::NmrOneD 51746 Specdb::NmrOneD 51747 Specdb::NmrOneD 51748 Specdb::NmrOneD 51749 Specdb::NmrOneD 51750 Specdb::NmrOneD 51751 Specdb::NmrOneD 51752 Specdb::NmrOneD 51753 Specdb::NmrOneD 51754 Specdb::NmrOneD 51755 Specdb::NmrOneD 51756 Specdb::NmrOneD 51757 Specdb::NmrOneD 51758 Specdb::NmrOneD 51759 Specdb::NmrOneD 51760 Specdb::NmrOneD 51761 Specdb::MsMs 28154 Specdb::MsMs 28155 Specdb::MsMs 28156 Specdb::MsMs 34712 Specdb::MsMs 34713 Specdb::MsMs 34714 Specdb::MsMs 2452708 Specdb::MsMs 2452709 Specdb::MsMs 2452710 Specdb::MsMs 2482123 Specdb::MsMs 2482124 Specdb::MsMs 2482125 25202908 C18239 PRECURSOR-Z Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. 21097882 Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. 22080510 Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. 18331064 Gutzke, G., Fischer, B., Mendel, R. R., Schwarz, G. (2001). "Thiocarboxylation of molybdopterin synthase provides evidence for the mechanism of dithiolene formation in metal-binding pterins." J Biol Chem 276:36268-36274. 11459846 Molybdopterin synthase sulfur carrier subunit P30748 MOAD_ECOLI moaD http://ecmdb.ca/proteins/P30748.xml Molybdopterin synthase catalytic subunit P30749 MOAE_ECOLI moaE http://ecmdb.ca/proteins/P30749.xml Molybdenum cofactor biosynthesis protein A P30745 MOAA_ECOLI moaA http://ecmdb.ca/proteins/P30745.xml Molybdenum cofactor biosynthesis protein C P0A738 MOAC_ECOLI moaC http://ecmdb.ca/proteins/P0A738.xml Guanosine triphosphate + Water <> Cyclic pyranopterin monophosphate + Pyrophosphate R09394 Cyclic pyranopterin monophosphate + Copper + 2 MoaD Protein with thiocarboxylate >5 Hydrogen ion +2 MoaD Protein with carboxylate + Molybdopterin Cyclic pyranopterin monophosphate + 2 Sulfur donor <> Molybdopterin R09395 Guanosine triphosphate > Cyclic pyranopterin monophosphate + Pyrophosphate RXN-8340 Cyclic pyranopterin monophosphate + Water + Thiocarboxylated-MPT-synthases > Molybdopterin + MPT-Synthases RXN-8342 Cyclic pyranopterin monophosphate + 2 [molybdopterin-synthase sulfur-carrier protein]-Gly-NH-CH(2)-C(O)SH + Water > molybdopterin forma +2 [molybdopterin-synthase sulfur-carrier protein] Guanosine triphosphate > Cyclic pyranopterin monophosphate + Pyrophosphate PW_R005152 Cyclic pyranopterin monophosphate + Water + thiocarboxylated small subunit of molybdopterin synthase >4 Hydrogen ion +2 thiocarboxylated small subunit of molybdopterin synthase + Molybdopterin + Molybdopterin PW_R005153 Cyclic pyranopterin monophosphate + 2 Sulfur donor <> Molybdopterin Guanosine triphosphate + Water <> Cyclic pyranopterin monophosphate + Pyrophosphate Cyclic pyranopterin monophosphate + 2 Sulfur donor <> Molybdopterin