1w4p
From Proteopedia
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'''BINDING OF NONNATURAL 3'-NUCLEOTIDES TO RIBONUCLEASE A''' | '''BINDING OF NONNATURAL 3'-NUCLEOTIDES TO RIBONUCLEASE A''' | ||
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[[Category: Sweeney, R Y.]] | [[Category: Sweeney, R Y.]] | ||
[[Category: Thiyagarajan, N.]] | [[Category: Thiyagarajan, N.]] | ||
| - | [[Category: | + | [[Category: Endonuclease]] |
| - | [[Category: | + | [[Category: Hydrolase]] |
| - | [[Category: | + | [[Category: Nonnatural 3'-nucleotide]] |
| - | [[Category: | + | [[Category: Ribonuclease]] |
| - | [[Category: | + | [[Category: Rnase some]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:09:11 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 10:09, 3 May 2008
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
1W4P is a Single protein structure of sequence from Bos taurus. 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 Sat May 3 13:09:11 2008
