 |
PDBsum entry 1eck
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Phosphotransferase
|
PDB id
|
|
|
|
1eck
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Solution structure of a hna-Rna hybrid.
|
|
|
Authors
|
|
E.Lescrinier,
R.Esnouf,
J.Schraml,
R.Busson,
H.Heus,
C.Hilbers,
P.Herdewijn.
|
|
|
Ref.
|
|
Chem Biol, 2000,
7,
719-731.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
BACKGROUND: Synthetic nucleic acid analogues with a conformationally restricted
sugar-phosphate backbone are widely used in antisense strategies for biomedical
and biochemical applications. The modified backbone protects the
oligonucleotides against degradation within the living cell, which allows them
to form stable duplexes with sequences in target mRNAs with the aim of arresting
their translation. The biologically most active antisense oligonucleotides also
trigger cleavage of the target RNA through activation of endogenous RNase H.
Systematic studies of synthetic oligonucleotides have also been conducted to
delineate the origin of the chirality of DNA and RNA that are both composed of
D-nucleosides. RESULTS: Hexitol nucleic acids (HNA) are the first example of
oligonucleotides with a six-membered carbohydrate moiety that can bind strongly
and selectively to complementary RNA oligomers. We present the first high
resolution nuclear magnetic resonance structure of a HNA oligomer bound to a
complementary RNA strand. The HNA-RNA complex forms an anti-parallel
heteroduplex and adopts a helical conformation that belongs to the A-type
family. Possibly, due to the rigidity of the rigid chair conformation of the
six-membered ring both the HNA and RNA strand in the duplex are well defined.
The observed absence of end-fraying effects also indicate a reduced
conformational flexibility of the HNA-RNA duplex compared to canonical dsRNA or
an RNA-DNA duplex. CONCLUSIONS: The P-P distance across the minor groove, which
is close to A-form, and the rigid conformation of the HNA-RNA complex, explain
its resistance towards degradation by Rnase H. The A-form character of the
HNA-RNA duplex and the reduced flexibility of the HNA strand is possibly
responsible for the stereoselectivity of HNA templates in non-enzymatic
replication of oligonucleotides, supporting the theory that nucleosides with
six-membered rings could have existed at some stage in molecular evolution.
|
|
|
|
|
|
|
|
Figure 2.
Figure 2. Schematic conformations of various
oligonucleotides. (a), HNA (1′-3′-dideoxy (4′→6′)
oligonucleotides), (b) RNA (ribose (5′→3′
oligonucleotides)), (c) hexopyranosyl (4′→6′)
oligonucleotide and (d) pentopyranosyl (2′→4′)
oligonucleotides. The resemblance between the hexitol ring and
the ribose can be seen by inserting a CH[2] group between the
O4′ and C1′ of the ribose. This is indicated by the dashed
line in the schematic RNA structure (b). Homo DNA is a chemical
analogue of (c), i.e. containing 2′-3′-dideoxy hexopyranosyl
(4′-6′) nucleotides.
|
|
Figure 5.
Figure 5. (a) Overlay of the ten structures closest to the
average of the final set of 25 structures. Superposition was
performed on residues 2–15. (b) Variation of the torsion
angles for the individual residues of the 25 final structures.
For comparison A- and B-form values are given by dashed and
dotted lines, respectively. The solid line indicates the average
value in the structure obtained previously by molecular modeling
[9].
|
|
|
|
|
|
The above figures are
reprinted
by permission from Cell Press:
Chem Biol
(2000,
7,
719-731)
copyright 2000.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
The closed conformation of a highly flexible protein: the structure of e. Coli adenylate kinase with bound AMP and amppnp.
|
|
|
Authors
|
|
M.B.Berry,
B.Meador,
T.Bilderback,
P.Liang,
M.Glaser,
G.N.Phillips.
|
|
|
Ref.
|
|
Proteins, 1994,
19,
183-198.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
