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1w4q
From Proteopedia
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BINDING OF NONNATURAL 3'-NUCLEOTIDES TO RIBONUCLEASE A
Overview
2'-Fluoro-2'-deoxyuridine 3'-phosphate (dU(F)MP) and arabinouridine, 3'-phosphate (araUMP) have non-natural furanose rings. dU(F)MP and araUMP, were prepared by chemical synthesis and found to have three- to sevenfold, higher affinity than uridine 3'-phosphate (3'-UMP) or 2'-deoxyuridine, 3'-phosphate (dUMP) for ribonuclease A (RNase A). These differences, probably arise (in part) from the phosphoryl groups of 3'-UMP, dU(F)MP, and araUMP (pK(a) = 5.9) being more anionic than that of dUMP (pK(a) =, 6.3). The three-dimensional structures of the crystalline complexes of, RNase A with dUMP, dU(F)MP and araUMP were determined at < 1.7 A, resolution by X-ray diffraction analysis. In these three structures, the, uracil nucleobases and phosphoryl groups bind to the enzyme in a nearly, identical position. Unlike 3'-UMP and dU(F)MP, dUMP and araUMP bind with, their furanose rings in the preferred pucker. In the RNase A.araUMP, complex, the 2'-hydroxyl group is exposed to the solvent. All four, 3'-nucleotides bind more tightly to wild-type RNase A than to its T45G, variant, which lacks the residue that interacts most closely with the, uracil nucleobase. These findings illuminate in atomic detail the, interaction of RNase A and 3'-nucleotides, and indicate that non-natural, furanose rings can serve as the basis for more potent inhibitors of, catalysis by RNase A.
About this Structure
1W4Q is a Single protein structure of sequence from Bos taurus with UMF as ligand. Active as Pancreatic ribonuclease, with EC number 3.1.27.5 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
Binding of non-natural 3'-nucleotides to ribonuclease A., Jenkins CL, Thiyagarajan N, Sweeney RY, Guy MP, Kelemen BR, Acharya KR, Raines RT, FEBS J. 2005 Feb;272(3):744-55. PMID:15670155
Page seeded by OCA on Mon Nov 5 15:37:46 2007
