1PF7

CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH IMMUCILLIN H

Summary for 1PF7

• Entry DOI: 10.2210/pdb1pf7/pdb
• Related: 1M73
• Descriptor: PURINE NUCLEOSIDE PHOSPHORYLASE, SULFATE ION, 1,4-DIDEOXY-4-AZA-1-(S)-(9-DEAZAHYPOXANTHIN-9-YL)-D-RIBITOL, ... (4 entities in total)
• Functional Keywords: purine nucleoside phosphorylase, drug design, synchrotron, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton (By similarity): P00491
• Total number of polymer chains: 1
• Total formula weight: 32739.32

Authors

De Azevedo Jr., W.F.,Canduri, F.,Dos Santos, D.M.,Pereira, J.H.,Dias, M.V.B.,Silva, R.G.,Mendes, M.A.,Palma, M.S.,Basso, L.A.,Santos, D.S. (deposition date: 2003-05-24, release date: 2004-06-01, Last modification date: 2023-09-20)

Primary citation

De Azevedo Jr., W.F.,Canduri, F.,Dos Santos, D.M.,Pereira, J.H.,Dias, M.V.B.,Silva, R.G.,Mendes, M.A.,Palma, M.S.,Basso, L.A.,Santos, D.S.
Structural basis for inhibition of human PNP by immucillin-H
Biochem.Biophys.Res.Commun., 309:917-922, 2003

PubMed Abstract: Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation. This work reports on the crystallographic study of the complex of human PNP-immucillin-H (HsPNP-ImmH) solved at 2.6A resolution using synchrotron radiation. Immucillin-H (ImmH) inhibits the growth of malignant T-cell lines in the presence of deoxyguanosine without affecting non-T-cell tumor lines. ImmH inhibits activated normal human T cells after antigenic stimulation in vitro. These biological effects of ImmH suggest that this agent may have utility in the treatment of certain human diseases characterized by abnormal T-cell growth or activation. This is the first structural report of human PNP complexed with immucillin-H. The comparison of the complex HsPNP-ImmH with recent crystallographic structures of human PNP explains the high specificity of immucillin-H for human PNP.

PubMed: 13679061
DOI: 10.1016/j.bbrc.2003.08.094

Experimental method

X-RAY DIFFRACTION (2.6 Å)