Stereochemistry of 2'-5' linked nucleic acids: crystal and molecular structure of ammonium adenylyl-2',5'-adenosine tetrahydrate: a core fragment of 2'-5' oligo A's produced by interferon induced adenylate synthetase.
The preponderance of 3'-5' phosphodiester links in nucleic acids is well known. Albeit less prevalent, the 2'-5' links are specifically utilised in the formation of 'lariat' in group II introns and in the msDNA-RNA junction in myxobacterium. As a sequel to our earlier study on cytidylyl-2',5'-adenosine we have now obtained the crystal structure of adenylyl-2',5'-adenosine (A2'p5'A) at atomic resolution. This dinucleoside monophosphate crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 7.956(3) A, b = 12.212(3) A and c = 36.654(3) A. CuK alpha intensity data were collected on a diffractometer. The structure was sloved by direct methods and refined by full matrix least squares methods to R = 10.8%. The 2' terminal adenine is in the commonly observed anti (chi 2 = 161 degrees) conformation and the 5' terminal base has a syn (chi 1 = 55 degrees) conformation more often seen in purine nucleotides. A noteworthy feature of A2'p5'A is the intranucleotide hydrogen bond between N3 and O5' atoms of the 5' adenine base. The two furanose rings in A2'p5'A show different conformations - C2' endo, C3' endo puckering for the 5' and 2' ends respectively. In this structure too there is a stacking of the purine base on the ribose O4' just as in other 2'-5' dinucleoside structures, a feature characteristically seen in the left handed Z DNA. In having syn, anti conformation about the glycosyl bonds, C2' endo, C3' endo mixed sugar puckering and N3-O5' intramolecular hydrogen bond A2'p5'A resembles its 3'-5' analogue and several other 2'-5' dinucleoside monophosphate structures solved so far. Striking similarities between the 2'-5' dinucleoside monophosphate structures suggest that the conformation of the 5'-end nucleoside dictates the conformation of the 2' end nucleoside. Also, the 2'-5' dimers do not favour formation of miniature classical double helical structures like the 3'-5' dimers. It is conceivable, 2-5(A) could be using the stereochemical features of A2'p5'A which accounts for its higher activity.
Krishnan
R
R
Department of Physics, Indian Institute of Science, Bangalore.
Seshadri
T P
TP
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000225:Adenine / Q000737:chemistry; D000227:Adenine Nucleotides / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D015226:Dinucleoside Phosphates / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009843:Oligoribonucleotides / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D009843:Oligoribonucleotides; C031130:adenylyl-(2'-5')-adenosine; C023505:2',5'-oligoadenylate; D004247:DNA; D015088:2',5'-Oligoadenylate Synthetase; D000225:Adenine