Summary information and primary citation
- PDB-id
-
3lwo;
SNAP-derived features in text and
JSON formats
- Class
- isomerase-RNA binding protein-RNA
- Method
- X-ray (2.855 Å)
- Summary
- Structure of h-aca rnp bound to a substrate RNA
containing 5bru
- Reference
-
Zhou J, Lv C, Liang B, Chen M, Yang W, Li H (2010):
"Glycosidic
bond conformation preference plays a pivotal role in
catalysis of RNA pseudouridylation: a combined simulation
and structural study." J.Mol.Biol.,
401, 690-695. doi: 10.1016/j.jmb.2010.06.061.
- Abstract
- The most abundant chemical modification on RNA is
isomerization of uridine (or pseudouridylation) catalyzed
by pseudouridine synthases. The catalytic mechanism of this
essential process remains largely speculative, partly due
to lack of knowledge of the pre-reactive state that is
important to the identification of reactive chemical
moieties. In the present study, we showed, using orthogonal
space random-walk free-energy simulation, that the
pre-reactive states of uridine and its reactive derivative
5-fluorouridine, bound to a ribonucleoprotein particle
pseudouridine synthase, strongly prefer the syn glycosidic
bond conformation, while that of the nonreactive
5-bromouridine-containing substrate is largely populated in
the anti conformation state. A high-resolution crystal
structure of the 5-bromouridine-containing substrate bound
to the ribonucleoprotein particle pseudouridine synthase
and enzyme activity assay confirmed the anti nonreactive
conformation and provided the molecular basis for its
confinement. The observed preference for the syn
pre-reactive state by the enzyme-bound uridine may help to
distinguish among currently proposed mechanisms.
