3INY
Crystal structure of human purine nucleoside phosphorylase in complex with 7-deazaguanine
Summary for 3INY
| Entry DOI | 10.2210/pdb3iny/pdb |
| Related | 1V41 |
| Descriptor | Purine nucleoside phosphorylase, SULFATE ION, 7-DEAZAGUANINE, ... (4 entities in total) |
| Functional Keywords | 7-deazaguanine, cytoskeleton, disease mutation, glycosyltransferase, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm, cytoskeleton (By similarity): P00491 |
| Total number of polymer chains | 1 |
| Total formula weight | 32623.20 |
| Authors | de Azevedo Jr, W.F.,Santos, D.S.,Basso, L.A. (deposition date: 2009-08-13, release date: 2011-01-19, Last modification date: 2023-09-06) |
| Primary citation | Caceres, R.A.,Timmers, L.F.,Pauli, I.,Gava, L.M.,Ducati, R.G.,Basso, L.A.,Santos, D.S.,de Azevedo, W.F. Crystal structure and molecular dynamics studies of human purine nucleoside phosphorylase complexed with 7-deazaguanine. J.Struct.Biol., 169:379-388, 2010 Cited by PubMed Abstract: In humans, purine nucleoside phosphorylase (HsPNP) is responsible for degradation of deoxyguanosine, and genetic deficiency of this enzyme leads to profound T-cell mediated immunosuppression. HsPNP is a target for inhibitor development aiming at T-cell immune response modulation. Here we report the crystal structure of HsPNP in complex with 7-deazaguanine (HsPNP:7DG) at 2.75 A. Molecular dynamics simulations were employed to assess the structural features of HsPNP in both free form and in complex with 7DG. Our results show that some regions, responsible for entrance and exit of substrate, present a conformational variability, which is dissected by dynamics simulation analysis. Enzymatic assays were also carried out and revealed that 7-deazaguanine presents a lower inhibitory activity against HsPNP (K(i)=200 microM). The present structure may be employed in both structure-based design of PNP inhibitors and in development of specific empirical scoring functions. PubMed: 19932753DOI: 10.1016/j.jsb.2009.11.010 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.75 Å) |
Structure validation
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