Balaji, PV and Rao, VSR and Saenger, W (1990) Computer Modeling Studies of Ribonuclease T,Guanosine Monophosphate Complexes. In: Biopolymers, 30 (34). pp. 257272.

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Abstract
The threedimensional 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 xray crystallographic studies of the $2^\prime$ GMPLys25RNase $T_1$ complex, where the inhibitor binds in C $2^\prime$ endo puckered conformation. These results are also in good agreement with the available 1Hnmr results of Inagaki et al. [(1985) Biochemistry 24, 10131020], 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 xray crystallographic and spectroscopic studies. An extensive hydrogenbonding scheme was predicted in all the three complexes. The hydrogenbonding scheme predicted for the $2^\prime$ GMP (C $2^\prime$ endo)RNase $T_1$ complex agrees well with those reported from xray 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 highsynrange 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 $2^\prime$ GMPRNase $T_1$ 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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