Structure of a 6-pyruvoyltetrahydropterin synthase homolog from Streptomyces coelicolor

Abstract

The X-ray crystal structure of the 6-pyruvoyltetrahydropterin synthase (PTPS) homolog from Streptomyces coelicolor, SCO 6650, was solved at 1.5 A resolution. SCO 6650 forms a hexameric T-fold that closely resembles other PTPS proteins. The biological activity of SCO 6650 is unknown, but it lacks both a required active-site zinc metal ion and the essential catalytic triad and does not catalyze the PTPS reaction. However, SCO 6650 maintains active-site residues consistent with binding a pterin-like substrate.

Figure 1

Summary of interactions between Rattus rattus PTPS and its substrate, 7,8-dihydroneopterin triphosphate (PDB code 1b66). The active site is composed of residues from three adjacent subunits (A, A′ and B). For each residue, the contributing subunit is indicated in red. Residues from the rat PTPS structure are in gray and the corresponding residues in SCO 6650 are shown in black. The residues that bind the pterin in rat PTPS (Glu133, Thr106, Val107 and Met70) are identical to those in SCO 6650.

Figure 2

The X-ray crystal structure of SCO 6650. The SCO 6650 hexamer observed across and down the T-fold barrel. Spheres represent residues highlighted in Fig. 1 ▶, demonstrating that three subunits contribute to the active site of the PTPS. The structural drawings were generated with PyMOL (DeLano, 2002 ▶).

Figure 3

A multiple sequence alignment of PTPS homologs from Py. horikoshii (gi:14590525), Ps. aeruginosa (gi:126031480), R. rattus (gi:4929886) and SCO 6650 generated with ClustalW (Thompson et al., 1994 ▶). The boxes in the alignment highlight the positions of the zinc-liganding histidine residues (Zn), the catalytic triad (Cat) and the substrate-binding residues (Sub) in PTPS.