dihydroneopterin aldolase; This model describes a bacterial dihydroneopterin aldolase, shown to form homo-octamers in E. coli. The equivalent activity is catalyzed by domains of larger folate biosynthesis proteins in other systems. The closely related parologous enzyme in E. coli, dihydroneopterin triphosphate epimerase, which is also homo-octameric, and dihydroneopterin aldolase domains of larger proteins, score below the trusted cutoff but may score well above the noise cutoff. [Biosynthesis of cofactors, prosthetic groups, and carriers, Folic acid]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 433666183    2 YVIRMKNCAFFARHGVLDEEEALGQRFYVDASLTVEPGRALVDDAIGETVNYGVAFTVIEEIITGHRRFLIEALALEVAK 81
Cdd:TIGR00525   1 DRVFIEGLEVFAYHGVFDHERVLGQRFVVDLELSVDETKAAESDDLGDTVNYAELYSAIEEIVAEKPRDLIETVAYRIAD 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 433666183   82 ALSGRFPQIRKAEVTVRKPNAPVPGVLDYVEVTVV 116
Cdd:TIGR00525  81 RLFADFPQVQRVKVRVSKPNAPIPGHLDDVSVEIR 115

dihydroneopterin aldolase; This model describes a bacterial dihydroneopterin aldolase, shown to form homo-octamers in E. coli. The equivalent activity is catalyzed by domains of larger folate biosynthesis proteins in other systems. The closely related parologous enzyme in E. coli, dihydroneopterin triphosphate epimerase, which is also homo-octameric, and dihydroneopterin aldolase domains of larger proteins, score below the trusted cutoff but may score well above the noise cutoff. [Biosynthesis of cofactors, prosthetic groups, and carriers, Folic acid]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 433666183    2 YVIRMKNCAFFARHGVLDEEEALGQRFYVDASLTVEPGRALVDDAIGETVNYGVAFTVIEEIITGHRRFLIEALALEVAK 81
Cdd:TIGR00525   1 DRVFIEGLEVFAYHGVFDHERVLGQRFVVDLELSVDETKAAESDDLGDTVNYAELYSAIEEIVAEKPRDLIETVAYRIAD 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 433666183   82 ALSGRFPQIRKAEVTVRKPNAPVPGVLDYVEVTVV 116
Cdd:TIGR00525  81 RLFADFPQVQRVKVRVSKPNAPIPGHLDDVSVEIR 115

Dihydroneopterin aldolase; This enzyme EC:4.1.2.25 catalyzes the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin in the biosynthetic pathway of tetrahydrofolate.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 433666183    4 IRMKNCAFFARHGVLDEEEALGQRFYVDASLTVEPGRALVDDAIGETVNYGVAFTVIEEIITGHRRFLIEALALEVAKAL 83
Cdd:pfam02152   1 IFIKGLRFYAYHGVYPEERRLGQRFVVDLELWLDLSKAAATDDLEDTVDYAEVYEAVKELVEGEPFKLLETLAERIADRL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 433666183   84 SGRFPQIRKAEVTVRKPNAPVPGVLDYVEVTV 115
Cdd:pfam02152  81 LEEFPGVEAVRVRVEKPNAPIPGPADSVGVEI 112

Dihydroneopterin aldolase (DHNA) and 7,8-dihydroneopterin triphosphate epimerase domain (DHNTPE); these enzymes have been designated folB and folX, respectively. Folate derivatives are essential cofactors in the biosynthesis of purines, pyrimidines, and amino acids, as well as formyl-tRNA. Mammalian cells are able to utilize pre-formed folates after uptake by a carrier-mediated active transport system. Most microbes and plants lack this system and must synthesize folates de novo from guanosine triphosphate. One enzyme from this pathway is DHNA which catalyses the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin in the biosynthetic pathway of tetrahydrofolate. Though it is known that DHNTPE catalyzes the epimerization of dihydroneopterin triphosphate to dihydromonapterin triphosphate, the biological role of this enzyme is still unclear. It is hypothesized that it is not an essential protein since a folX knockout in E. coli has a normal phenotype and the fact that folX is not present in H. influenza. In addition both enzymes have been shown to be able to compensate for the other's activity albeit at slower reaction rates. The functional enzyme for both is an octamer of identical subunits. Mammals lack many of the enzymes in the folate pathway including, DHNA and DHNTPE.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 433666183   1 MYVIRMKNCAFFARHGVLDEEEALGQRFYVDASLTVEPGRALVDDAIGETVNYGVAFTVIEEIITGHRRFLIEALALEVA 80
Cdd:cd00534    1 MDRVFIKGLRFYTIHGVFEEERLLGQKFVVDLTLWYDLSKAGESDDLADTLNYAEVAKLIKKIVEGSPFKLIETLAEEIA 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 433666183  81 KALSGRFPQIRKAEVTVRKPNAPVPGVLDYVEVTVVW 117
Cdd:cd00534   81 DILLEDYPKVSAIKVKVEKPNAPIPASADGVGVEIER 117

dihydroneopterin aldolase; This model describes a bacterial dihydroneopterin aldolase, shown to form homo-octamers in E. coli. The equivalent activity is catalyzed by domains of larger folate biosynthesis proteins in other systems. The closely related parologous enzyme in E. coli, dihydroneopterin triphosphate epimerase, which is also homo-octameric, and dihydroneopterin aldolase domains of larger proteins, score below the trusted cutoff but may score well above the noise cutoff. [Biosynthesis of cofactors, prosthetic groups, and carriers, Folic acid]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 433666183    2 YVIRMKNCAFFARHGVLDEEEALGQRFYVDASLTVEPGRALVDDAIGETVNYGVAFTVIEEIITGHRRFLIEALALEVAK 81
Cdd:TIGR00525   1 DRVFIEGLEVFAYHGVFDHERVLGQRFVVDLELSVDETKAAESDDLGDTVNYAELYSAIEEIVAEKPRDLIETVAYRIAD 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 433666183   82 ALSGRFPQIRKAEVTVRKPNAPVPGVLDYVEVTVV 116
Cdd:TIGR00525  81 RLFADFPQVQRVKVRVSKPNAPIPGHLDDVSVEIR 115

Dihydroneopterin aldolase; This enzyme EC:4.1.2.25 catalyzes the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin in the biosynthetic pathway of tetrahydrofolate.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 433666183    4 IRMKNCAFFARHGVLDEEEALGQRFYVDASLTVEPGRALVDDAIGETVNYGVAFTVIEEIITGHRRFLIEALALEVAKAL 83
Cdd:pfam02152   1 IFIKGLRFYAYHGVYPEERRLGQRFVVDLELWLDLSKAAATDDLEDTVDYAEVYEAVKELVEGEPFKLLETLAERIADRL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 433666183   84 SGRFPQIRKAEVTVRKPNAPVPGVLDYVEVTV 115
Cdd:pfam02152  81 LEEFPGVEAVRVRVEKPNAPIPGPADSVGVEI 112

Dihydroneopterin aldolase (DHNA) and 7,8-dihydroneopterin triphosphate epimerase domain (DHNTPE); these enzymes have been designated folB and folX, respectively. Folate derivatives are essential cofactors in the biosynthesis of purines, pyrimidines, and amino acids, as well as formyl-tRNA. Mammalian cells are able to utilize pre-formed folates after uptake by a carrier-mediated active transport system. Most microbes and plants lack this system and must synthesize folates de novo from guanosine triphosphate. One enzyme from this pathway is DHNA which catalyses the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin in the biosynthetic pathway of tetrahydrofolate. Though it is known that DHNTPE catalyzes the epimerization of dihydroneopterin triphosphate to dihydromonapterin triphosphate, the biological role of this enzyme is still unclear. It is hypothesized that it is not an essential protein since a folX knockout in E. coli has a normal phenotype and the fact that folX is not present in H. influenza. In addition both enzymes have been shown to be able to compensate for the other's activity albeit at slower reaction rates. The functional enzyme for both is an octamer of identical subunits. Mammals lack many of the enzymes in the folate pathway including, DHNA and DHNTPE.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 433666183   1 MYVIRMKNCAFFARHGVLDEEEALGQRFYVDASLTVEPGRALVDDAIGETVNYGVAFTVIEEIITGHRRFLIEALALEVA 80
Cdd:cd00534    1 MDRVFIKGLRFYTIHGVFEEERLLGQKFVVDLTLWYDLSKAGESDDLADTLNYAEVAKLIKKIVEGSPFKLIETLAEEIA 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 433666183  81 KALSGRFPQIRKAEVTVRKPNAPVPGVLDYVEVTVVW 117
Cdd:cd00534   81 DILLEDYPKVSAIKVKVEKPNAPIPASADGVGVEIER 117

Tunnelling fold (T-fold). The five known T-folds are found in five different enzymes with different functions: dihydroneopterin-triphosphate epimerase (DHNTPE), dihydroneopterin aldolase (DHNA) , GTP cyclohydrolase I (GTPCH-1), 6-pyrovoyl tetrahydropterin synthetase (PTPS), and uricase (UO,uroate/urate oxidase). They bind to substrates belonging to the purine or pterin families, and share a fold-related binding site with a glutamate or glutamine residue anchoring the substrate and a lot of conserved interactions. They also share a similar oligomerization mode: several T-folds join together to form a beta(2n)alpha(n) barrel, then two barrels join together in a head-to-head fashion to made up the native enzymes. The functional enzyme is a tetramer for UO, a hexamer for PTPS, an octamer for DHNA/DHNTPE and a decamer for GTPCH-1. The substrate is located in a deep and narrow pocket at the interface between monomers. In PTPS, the active site is located at the interface of three monomers, two from one trimer and one from the other trimer. In GTPCH-1, it is also located at the interface of three subunits, two from one pentamer and one from the other pentamer. There are four equivalent active sites in UO, six in PTPS, eight in DHNA/DHNTPE and ten in GTPCH-1. Each globular multimeric enzyme encloses a tunnel which is lined with charged residues for DHNA and UO, and with basic residues in PTPS. The N and C-terminal ends are located on one side of the T-fold while the residues involved in the catalytic activity are located at the opposite side. In PTPS, UO and DHNA/DHNTPE, the N and C-terminal extremities of the enzyme are located on the exterior side of the functional multimeric enzyme. In GTPCH-1, the extra C-terminal helix places the extremity inside the tunnel.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 433666183   1 MYVIRMKNCAFFARHGVLDEEEALGQRFYVDASLTVEPGRALVDDAIGETVNYGVAFTVIEEIITGHRrfLIEALALEVA 80
Cdd:cd00651    1 TDGVRVKDLLKVTRLGFVTLERTVGQIFEVDVTLSWDGKKAAASDDVATDTVYNTIYRLAKEYVEGSQ--LIERLAEEIA 78

                         90       100       110
                 ....*....|....*....|....*....|.
gi 433666183  81 KALSGRFP-QIRKAEVTVRKPNAPVPGVLDY 110
Cdd:cd00651   79 YLIAEHFLsSVAEVKVEEKKPHAVIPDRGVF 109