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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2270222099   1 MVMNLTDLKEYMEEAIMKPLDHKNLDLDVPYFADAVSTTENVAVYIWESLQKLLPVGALYKVKVFETDNNIVVYKGE 77
Cdd:cd00470    59 MVMNLTDLKKAIEEAIMKPLDHKNLDDDVPYFADVVSTTENLAVYIWDNLQKVLPVGLLYEVKVHETDKNIVVYRGE 135

6-pyruvoyl tetrahydropterin synthase (PTPS). 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 PTPS which catalyzes the conversion of dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin. The functional enzyme is a hexamer of identical subunits.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2270222099   1 MVMNLTDLKEYMEEAIMKPLDHKNLDLDVPYFADAVSTTENVAVYIWESLQKLLPVGALYKVKVFETDNNIVVYKGE 77
Cdd:cd00470    59 MVMNLTDLKKAIEEAIMKPLDHKNLDDDVPYFADVVSTTENLAVYIWDNLQKVLPVGLLYEVKVHETDKNIVVYRGE 135

6-pyruvoyl tetrahydropterin synthase; 6-Pyruvoyl tetrahydrobiopterin synthase catalyzes the conversion of dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin, the second of three enzymatic steps in the synthesis of tetrahydrobiopterin from GTP. The functional enzyme is a hexamer of identical subunits.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2270222099   1 MVMNLTDLKEYMEEaIMKPLDHKNLDlDVPYFADAVSTTENVAVYIWESLQKLL--PVGALYKVKVFETDNNIVVYKGE 77
Cdd:pfam01242  45 MVVDFGELKKAVKE-VLDRLDHRFLN-DDPEFETLNPTAENLARYIFERLKPRLsgGGVRLARVRVWETPTSWAEYRGE 121

6-pyruvoyl tetrahydropterin synthase (PTPS). 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 PTPS which catalyzes the conversion of dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin. The functional enzyme is a hexamer of identical subunits.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2270222099   1 MVMNLTDLKEYMEEAIMKPLDHKNLDLDVPYFADAVSTTENVAVYIWESLQKLLPVGALYKVKVFETDNNIVVYKGE 77
Cdd:cd00470    59 MVMNLTDLKKAIEEAIMKPLDHKNLDDDVPYFADVVSTTENLAVYIWDNLQKVLPVGLLYEVKVHETDKNIVVYRGE 135

6-pyruvoyl tetrahydropterin synthase; 6-Pyruvoyl tetrahydrobiopterin synthase catalyzes the conversion of dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin, the second of three enzymatic steps in the synthesis of tetrahydrobiopterin from GTP. The functional enzyme is a hexamer of identical subunits.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2270222099   1 MVMNLTDLKEYMEEaIMKPLDHKNLDlDVPYFADAVSTTENVAVYIWESLQKLL--PVGALYKVKVFETDNNIVVYKGE 77
Cdd:pfam01242  45 MVVDFGELKKAVKE-VLDRLDHRFLN-DDPEFETLNPTAENLARYIFERLKPRLsgGGVRLARVRVWETPTSWAEYRGE 121

queuosine biosynthesis protein QueD; Members of this protein family, closely related to eukaryotic 6-pyruvoyl tetrahydrobiopterin synthase enzymes, are the QueD protein of queuosine biosynthesis. Queuosine is a hypermodified base in the wobble position of tRNAs for Tyr, His, Asp, and Asn in many species. This modification, although widespread, appears not to be important for viability. The queuosine precursor made by this enzyme may be converted instead to archeaosine as in some Archaea. [Protein synthesis, tRNA and rRNA base modification]

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                 ....*....|....*....|....*....|....*....|....*....|
gi 2270222099  1 MVMNLTDLKEYMEEaIMKPLDHKNLdLDVPYFADavSTTENVAVYIWESL 50
Cdd:TIGR03367 44 MVMDFSDLKAIVKE-VVDRLDHALL-NDVLGLEN--PTAENLARWIYDRL 89