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1pf7

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Revision as of 16:36, 12 November 2007 by OCA (Talk | contribs)
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1pf7, resolution 2.60Å

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CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH IMMUCILLIN H

Contents

Overview

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.

Disease

Known diseases associated with this structure: Neutral lipid storage disease with myopathy OMIM:[609059], Nucleoside phosphorylase deficiency, immunodeficiency due to OMIM:[164050]

About this Structure

1PF7 is a Single protein structure of sequence from Homo sapiens with SO4 and IMH as ligands. Active as Purine-nucleoside phosphorylase, with EC number 2.4.2.1 Full crystallographic information is available from OCA.

Reference

Structural basis for inhibition of human PNP by immucillin-H., Filgueira de Azevedo W Jr, Canduri F, Marangoni dos Santos D, Pereira JH, Dias MV, Silva RG, Mendes MA, Basso LA, Palma MS, Santos DS, Biochem Biophys Res Commun. 2003 Oct 3;309(4):917-22. PMID:13679061

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