1vfn: Difference between revisions

Trimeric calf spleen purine nucleoside phosphorylase has been complexed, with hypoxanthine via phosphorolysis of inosine in the presence of, phosphate. The resulting, "Michaelis" complex (three hypoxanthine, molecules per trimer), presumed to be formed under these conditions, crystallized in the cubic space group P2(1)3, with unit cell dimension a =, 94.11 A and one monomer in the asymmetric crystal unit; the biologically, active trimer is located on the crystallographic 3-fold axis., High-resolution X-ray diffraction data were collected using synchrotron, radiation (EMBL outstation, Hamburg, c/o DESY). The crystal structure has, been determined by molecular replacement and refined at 2.15 A resolution, to an R-value of 0.18. In the hypoxanthine binding site, a cis-peptide, bond between Asn243 and Lys244 is observed. Side-chains of GIu201 and, Asn243, as well as one integral water molecule located in the base binding, site, form hydrogen bonds with the hypoxanthine N-1 H, N-7 H and O-6. A, second water molecule links the base positions N-3 and N-9 with an, adjacent pocket, which presumably is the phosphate-binding site. This, pocket is filled completely by a cluster of six water molecules. Hence all, possible donor/acceptor-positions of hypoxanthine are saturated by, hydrogen-bonding to protein side-chains or integral water molecules., Purine nucleoside phosphorylase isolated form human tissues is a primary, target for chemotherapeutic intervention, and the more stable calf enzyme, has similar physico-chemical and kinetic properties, as well as response, to inhibitors. Hence the high-resolution structure presented here may, serve for design of inhibitors with potential pharmacological, applications.

1VFN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with MG, ZN and HPA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] Structure known Active Sites: BAS and PRE. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1VFN OCA].  

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