-
6
-
-
2242459926
-
-
note
-
Materials and Methods are available as supporting online material on Science Online.
-
-
-
-
8
-
-
0032503565
-
-
B. D. Wladkowski, L. A. Svensson, L. Sjolin, J. E. Ladner, G. L. Gilliland, J. Am. Chem. Soc. 120, 5488 (1998).
-
(1998)
J. Am. Chem. Soc.
, vol.120
, pp. 5488
-
-
Wladkowski, B.D.1
Svensson, L.A.2
Sjolin, L.3
Ladner, J.E.4
Gilliland, G.L.5
-
16
-
-
2242455445
-
-
note
-
All-atom superposition of the nucleobases of G8, A9, and A38 (31 atoms) gives root mean square (rms) differences of 0.32 A and 0.31 A for the precursor versus the transition state mimic, and the transition state mimic versus the product, respectively.
-
-
-
-
21
-
-
0035890245
-
-
R. Pinard et al., EMBO J. 20, 6434 (2001).
-
(2001)
EMBO J.
, vol.20
, pp. 6434
-
-
Pinard, R.1
-
22
-
-
2242453665
-
-
note
-
It has also been shown that deletion or methylation of the exocyclic amino group of G8 is deleterious for catalysis (1, 21, 24). This functional group hydrogen bonds to a nonbridging phosphate oxygen in both the precursor and the transition state (Figs. 1D, 2A, and 3).
-
-
-
-
25
-
-
0034757632
-
-
S. P. Ryder et al., RNA 7, 1454 (2001).
-
(2001)
RNA
, vol.7
, pp. 1454
-
-
Ryder, S.P.1
-
26
-
-
2242490419
-
-
note
-
When examined with the use of a stable RNA construct, the only adenosine functional group that interferes with ribozyme activity is the exocyclic amine of A38, and this interference is independent of pH (25). In both transition state and product, this amine donates a hydrogen bond to a nonbridging phosphate oxygen (Figs. 1D, 2A, and 3). In a destabilized construct, the exocyclic amine of A9 shows a pH-independent interference (25). This can be explained by the hydrogen bond it makes to the transition state (Figs. 1D and 3B).
-
-
-
-
28
-
-
2242467977
-
-
note
-
The ribozyme may also destabilize the precursor by desolvating the scissile phosphate and not saturating the partially buried anion with hydrogen bonds.
-
-
-
-
30
-
-
0029008042
-
-
G. J. Narlikar, V. Gopalakrishnan, T. S. McConnell, N. Usman, D. Herschlag, Proc. Natl. Acad. Sci. U.S.A. 92, 3668 (1995).
-
(1995)
Proc. Natl. Acad. Sci. U.S.A.
, vol.92
, pp. 3668
-
-
Narlikar, G.J.1
Gopalakrishnan, V.2
McConnell, T.S.3
Usman, N.4
Herschlag, D.5
-
31
-
-
0030744201
-
-
K. J. Hertel, A. Peracchi, O. C. Uhlenbeck, D. Herschlag, Proc. Natl. Acad. Sci. U.S.A. 94, 8497 (1997).
-
(1997)
Proc. Natl. Acad. Sci. U.S.A.
, vol.94
, pp. 8497
-
-
Hertel, K.J.1
Peracchi, A.2
Uhlenbeck, O.C.3
Herschlag, D.4
-
36
-
-
0025335881
-
-
H. van Tol, J. M. Buzayan, P. A. Feldstein, F. Eckstein, G. Bruening, Nucleic Acids. Res. 18, 1971 (1990).
-
(1990)
Nucleic Acids Res.
, vol.18
, pp. 1971
-
-
Van Tol, H.1
Buzayan, J.M.2
Feldstein, P.A.3
Eckstein, F.4
Bruening, G.5
-
38
-
-
2242495792
-
-
note
-
We thank the staff of beamlines 5.0.1 and 5.0.2 of the Advanced Light Source (ALS), Lawrence Berkeley National Laboratory, for data collection support; J. Bolduc, P. Heath, and B. Shen for crystallographic and computational support; P. Gafken for mass spectrometry; and J. Simon, B. Stoddard, and G. Varani for discussions. This work was supported by the NIH (grants GM63576 and RR15943 to A.R.F. and GM56947 to S.Th.S.). P.B.R. is a postdoctoral trainee of the Chromosome Metabolism and Cancer training grant from the National Cancer Institute to the Fred Hutchinson Cancer Research Center (FHCRC). Access to ALS beamlines 5.0.1 and 5.0.2 as part of the principal research consortium was funded by general support from the FHCRC. A.R.F. is a Rita Allen Foundation Scholar. Coordinates and structure factors have been deposited with the Protein Data Bank (accession codes 1M5K, 1M50, 1M5V, and 1M5P for the methoxy, vanadate, all-RNA, and 5′-chloro structures, respectively).
-
-
-
|