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Computer Modeling Studies of Ribonuclease T,-Guanosine Monophosphate Complexes

Balaji, PV and Rao, VSR and Saenger, W (1990) Computer Modeling Studies of Ribonuclease T,-Guanosine Monophosphate Complexes. In: Biopolymers, 30 (3-4). pp. 257-272.


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The three-dimensional structures of ribonuclease (RNase) $T_1$ complexes with the inhibitors $2^\prime$ -guanylic acid ($2^\prime$ -GMP), $3^\prime$ -guanylic acid ($3^\prime$ -GMP), and $5^\prime$ -guanylic acid ($5^\prime$ -GMP) were predicted by energy minimization studies. It is shown that these inhibitors can bind to RNase $T_1$ in either of the ribose puckered conformations (C $2^\prime$ -endo and C $3^\prime$ -endo) in solid state and exist in significant amounts in both forms in solution. These studies are in agreement with the x-ray crystallographic studies of the $2^\prime$ -GMP-Lys25-RNase $T_1$ complex, where the inhibitor binds in C $2^\prime$ -endo puckered conformation. These results are also in good agreement with the available 1H-nmr results of Inagaki et al. [(1985) Biochemistry 24, 1013-1020], but differ from their conclusions where the authors favor only the C $3^\prime$ -endo ribose conformation for all the three inhibitors. The calculations explain the apparent discrepancies in the conclusions drawn by x-ray crystallographic and spectroscopic studies. An extensive hydrogen-bonding scheme was predicted in all the three complexes. The hydrogen-bonding scheme predicted for the $2^\prime$ -GMP (C $2^\prime$ -endo)-RNase $T_1$ complex agrees well with those reported from x-ray crystallographic studies. In all three complexes the base and the phosphate bind in nearly identical sites independent of the position of the phosphate or the ribose pucker. The glycosyl torsion angle favors a value in the +syn range in the $2^\prime$ -GMP(C $2^\prime$ -endo)-RNase $T_1$, $3^\prime$ -GMP(C $2^\prime$ -endo)-RNase $T_1$, and $3^\prime$ -GMP(C $2^\prime$ -endo)-RNase $T_1$ complexes; in the high-synrange in the $2^\prime$ -GMP(C3?-endo)-RNase $T_1$ complex; and in the -syn range in the $5^\prime$ -GMP(C $2^\prime$ -endo)-RNase $T_1$, and $5^\prime$ GMP(C $3^\prime$ -endo)-RNase $T_1$ complexes. These results are in agreement with experimental studies showing that the inhibitory power decreases in the order $2^\prime$ -GMP > $3^\prime$ -GMP > $5^\prime$ -GMP, and they also explain the high $pK_a$ value observed for Glu58 in the $2^\prime$ -GMP-RNase $T_1$ complex.

Item Type: Journal Article
Publication: Biopolymers
Publisher: John Wiley & Sons, Inc.
Additional Information: The copyright belongs to John Wiley & Sons, Inc.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 30 Nov 2005
Last Modified: 19 Sep 2010 04:21
URI: http://eprints.iisc.ac.in/id/eprint/4102

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