3IX2

CRYSTAL STRUCTURE OF PURINE NUCLEOSIDE PHOSPHORYLASE FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH ACYCLOVIR

Summary for 3IX2

• Entry DOI: 10.2210/pdb3ix2/pdb
• Related: 1N3I 1PWY
• Descriptor: Purine nucleoside phosphorylase, PHOSPHATE ION, 9-HYROXYETHOXYMETHYLGUANINE, ... (4 entities in total)
• Functional Keywords: mycobacterium tuberculosis, purine nucleoside phosphorylase, acyclovir, transferase
• Biological source: Mycobacterium tuberculosis variant bovis AF2122/97
• Total number of polymer chains: 3
• Total formula weight: 83758.90

Authors

de Azevedo Jr., W.F.,Basso, L.A.,Santos, D.S. (deposition date: 2009-09-03, release date: 2021-07-21, Last modification date: 2023-09-20)

Primary citation

Caceres, R.A.,Timmers, L.F.,Ducati, R.G.,da Silva, D.O.,Basso, L.A.,de Azevedo Jr., W.F.,Santos, D.S.
Crystal structure and molecular dynamics studies of purine nucleoside phosphorylase from Mycobacterium tuberculosis associated with acyclovir.
Biochimie, 94:155-165, 2012

PubMed Abstract: Consumption has been a scourge of mankind since ancient times. This illness has charged a high price to human lives. Many efforts have been made to defeat Mycobacterium tuberculosis (Mt). The M. tuberculosis purine nucleoside phosphorylase (MtPNP) is considered an interesting target to pursuit new potential inhibitors, inasmuch it belongs to the purine salvage pathway and its activity might be involved in the mycobacterial latency process. Here we present the MtPNP crystallographic structure associated with acyclovir and phosphate (MtPNP:ACY:PO(4)) at 2.10 Å resolution. Molecular dynamics simulations were carried out in order to dissect MtPNP:ACY:PO(4) structural features, and the influence of the ligand in the binding pocket stability. Our results revealed that the ligand leads to active site lost of stability, in agreement with experimental results, which demonstrate a considerable inhibitory activity against MtPNP (K(i) = 150 nM). Furthermore, we observed that some residues which are important in the proper ligand's anchor into the human homologous enzyme do not present the same importance to MtPNP. Therewithal, these findings contribute to the search of new specific inhibitors for MtPNP, since peculiarities between the mycobacterial and human enzyme binding sites have been identified, making a structural-based drug design feasible.

PubMed: 22033138
DOI: 10.1016/j.biochi.2011.10.003

Experimental method

X-RAY DIFFRACTION (2.1 Å)