3T8I: Structural Analysis Of Thermostable S. Solfataricus Purine-Specific Nucleoside Hydrolase

The purine- and pyrimidine-specific nucleoside hydrolases (NHs) from the archaeon Sulfolobus solfataricus participate in the fundamental pathway of nucleotide catabolism and function to maintain adequate levels of free nitrogenous bases for cellular function. The two highly homologous isozymes display distinct specificities toward nucleoside substrates, and both lack the amino acids employed for activation of the leaving group in the hydrolytic reaction by the NHs characterized thus far. We determined the high-resolution crystal structures of the purine- and pyrimidine-specific NHs from S. solfataricus to reveal that both enzymes belong to NH structural homology group I, despite the different substrate specificities. A Na(+) ion is bound at the active site of the pyrimidine-specific NH instead of the prototypical Ca(2+), delineating a role of the metals in the catalytic mechanism of NHs in the substrate binding rather than nucleophile activation. A conserved His residue, which regulates product release in other homologous NHs, provides crucial interactions for leaving group activation in the archaeal isozymes. Modeling of the enzyme-substrate interactions suggests that steric exclusion and catalytic selection underlie the orthogonal base specificity of the two isozymes.
PDB ID: 3T8IDownload
MMDB ID: 99653
PDB Deposition Date: 2011/8/1
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 3T8I: tetrameric; determined by author and by software (PISA)
Molecular Components in 3T8I
Label Count Molecule
Proteins (4 molecules)
Purine Nucleosidase, (Iunh-2)
Molecule annotation
Chemicals (27 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB