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| - | [[Image:1w4p.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1w4p| PDB=1w4p | SCENE= }} | | {{STRUCTURE_1w4p| PDB=1w4p | SCENE= }} |
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| - | '''BINDING OF NONNATURAL 3'-NUCLEOTIDES TO RIBONUCLEASE A'''
| + | ===BINDING OF NONNATURAL 3'-NUCLEOTIDES TO RIBONUCLEASE A=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_15670155}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15670155 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15670155}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Ribonuclease]] | | [[Category: Ribonuclease]] |
| | [[Category: Rnase some]] | | [[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 Mon Jul 28 21:00:55 2008'' |
Revision as of 18:01, 28 July 2008
Template:STRUCTURE 1w4p
BINDING OF NONNATURAL 3'-NUCLEOTIDES TO RIBONUCLEASE A
Template:ABSTRACT PUBMED 15670155
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 Mon Jul 28 21:00:55 2008
