Download MendeleyStructures of human cytosolic and mitochondrial nucleotidases: implications for structure-based design of selective inhibitors.
Pachl, P., Fabry, M., Rosenberg, I., Simak, O., Rezacova, P., Brynda, J.(2014) Acta Crystallogr D Biol Crystallogr 70: 461-470
- PubMed: 24531480
- DOI: https://doi.org/10.1107/S1399004713030502
- Primary Citation of Related Structures:
4L57, 4L6A - PubMed Abstract:
The human 5'(3')-deoxyribonucleotidases catalyze the dephosphorylation of deoxyribonucleoside monophosphates to the corresponding deoxyribonucleosides and thus help to maintain the balance between pools of nucleosides and nucleotides. Here, the structures of human cytosolic deoxyribonucleotidase (cdN) at atomic resolution (1.08 Å) and mitochondrial deoxyribonucleotidase (mdN) at near-atomic resolution (1.4 Å) are reported. The attainment of an atomic resolution structure allowed interatomic distances to be used to assess the probable protonation state of the phosphate anion and the side chains in the enzyme active site. A detailed comparison of the cdN and mdN active sites allowed the design of a cdN-specific inhibitor.
Organizational Affiliation:
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, 166 37 Prague 6, Czech Republic.
