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Default Three-dimensional structure of the complexes of ribonuclease A with 2',5'-CpA and 3',

Three-dimensional structure of the complexes of ribonuclease A with 2',5'-CpA and 3',5'-d(CpA) in aqueous solution, as obtained by NMR and restrained molecular dynamics.

Related Articles Three-dimensional structure of the complexes of ribonuclease A with 2',5'-CpA and 3',5'-d(CpA) in aqueous solution, as obtained by NMR and restrained molecular dynamics.

Protein Sci. 1996 Aug;5(8):1633-47

Authors: Toiron C, González C, Bruix M, Rico M

The three-dimensional structure of the complexes of ribonuclease A with cytidyl-2',5'-adenosine (2',5'-CpA) and deoxycytidyl-3',5'-deoxyadenosine [3',5'-d(CpA)] in aqueous solution has been determined by 1H NMR methods in combination with restrained molecular dynamics calculations. Twenty-three intermolecular NOE cross-corrections for the 3',5'-d(CpA) complex and 19 for the 2',5'-CpA, together with about 1,000 intramolecular NOEs assigned for each complex, were translated into distance constraints and used in the calculation. No significant changes in the global structure of the enzyme occur upon complex formation. The side chains of His 12, Thr 45, His 119, and the amide backbone group of Phe 120 are involved directly in the binding of the ligands at the active site. The conformation of the two bases is anti in the two complexes, but differs from the crystal structure in the conformation of the two sugar rings in 3',5'-d(CpA), shown to be in the S-type region, as deduced from an analysis of couplings between the ribose protons. His 119 is found in the two complexes in only one conformation, corresponding to position A in the free protein. Side chains of Asn 67, Gln 69, Asn 71, and Glu 111 from transient hydrogen bonds with the adenine base, showing the existence of a pronounced flexibility of these enzyme side chains at the binding site of the downstream adenine. All other general features on the structures coincide clearly with those observed in the crystal state.

PMID: 8844852 [PubMed - indexed for MEDLINE]



Source: PubMed
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