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1w4p
From Proteopedia
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==Overview== | ==Overview== | ||
| - | 2'-Fluoro-2'-deoxyuridine 3'-phosphate (dU(F)MP) and arabinouridine | + | 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== | ==About this Structure== | ||
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[[Category: Pancreatic ribonuclease]] | [[Category: Pancreatic ribonuclease]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Acharya, K | + | [[Category: Acharya, K R.]] |
| - | [[Category: Guy, M | + | [[Category: Guy, M P.]] |
| - | [[Category: Jenkins, C | + | [[Category: Jenkins, C L.]] |
| - | [[Category: Kelemen, B | + | [[Category: Kelemen, B R.]] |
| - | [[Category: Raines, R | + | [[Category: Raines, R T.]] |
| - | [[Category: Sweeney, R | + | [[Category: Sweeney, R Y.]] |
[[Category: Thiyagarajan, N.]] | [[Category: Thiyagarajan, N.]] | ||
[[Category: UM3]] | [[Category: UM3]] | ||
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[[Category: rnase a]] | [[Category: rnase a]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:40:26 2008'' |
Revision as of 13:40, 21 February 2008
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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
1W4P is a Single protein structure of sequence from Bos taurus with as ligand. Active as Pancreatic ribonuclease, with EC number 3.1.27.5 Known structural/functional Site: . 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 Thu Feb 21 15:40:26 2008
