 |
PDBsum entry 1obt
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.3.2.2.22
- rRNA N-glycosylase.
|
|
|
|
|
|
|
Reaction:
|
|
Endohydrolysis of the N-glycosidic bond at one specific adenosine on the 28S rRNA.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Biochemistry
35:11098-11103
(1996)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structure and activity of an active site substitution of ricin A chain.
|
|
P.J.Day,
S.R.Ernst,
A.E.Frankel,
A.F.Monzingo,
J.M.Pascal,
M.C.Molina-Svinth,
J.D.Robertus.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The A chain of ricin (RTA) is an N-glycosidase which inactivates ribosomes by
removing a single adenine base from a conserved region of rRNA. X-ray structures
and site-directed mutagenesis revealed that Arg 180 interacts with the target
adenine hydrogen bonding with N3. It may fully or partially protonate that atom
as part of the hydrolysis mechanism. Arg 180 was previously converted to His
(R180H) and shown to greatly reduce activity. Here R180H is shown to reduce
overall activity 500-fold against Artemia salina ribosomes. A 2.2 A crystal
structure reveals the mutation causes a rearrangement of the active site cleft,
with Tyr 80 moving to block access to the adenine recognition site. His 180
forms a strong aromatic interaction with Trp 211, Tyr 80, and Tyr 123. A complex
is formed with 250 mM AMP. The nucleotide binds in the active site region, but
in an apparently nonproductive orientation. His 180 cannot bond to N3 and is
screened from the substrate analog by the intervening Tyr 80. It may be that
natural polynucleotide substrates, using additional interactions, can displace
Tyr 80 and effect a productive binding.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
J.H.Carra,
C.A.McHugh,
S.Mulligan,
L.M.Machiesky,
A.S.Soares,
and
C.B.Millard
(2007).
Fragment-based identification of determinants of conformational and spectroscopic change at the ricin active site.
|
| |
BMC Struct Biol,
7,
72.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
N.A.Jolliffe,
A.Di Cola,
C.J.Marsden,
J.M.Lord,
A.Ceriotti,
L.Frigerio,
and
L.M.Roberts
(2006).
The N-terminal ricin propeptide influences the fate of ricin A-chain in tobacco protoplasts.
|
| |
J Biol Chem,
281,
23377-23385.
|
|
|
|
|
|
|
C.J.Marsden,
D.C.Smith,
L.M.Roberts,
and
J.M.Lord
(2005).
Ricin: current understanding and prospects for an antiricin vaccine.
|
| |
Expert Rev Vaccines,
4,
229-237.
|
|
|
|
|
|
|
C.L.Zhou,
A.T.Zemla,
D.Roe,
M.Young,
M.Lam,
J.S.Schoeniger,
and
R.Balhorn
(2005).
Computational approaches for identification of conserved/unique binding pockets in the A chain of ricin.
|
| |
Bioinformatics,
21,
3089-3096.
|
|
|
|
|
|
|
V.Mishra,
S.Bilgrami,
R.S.Sharma,
P.Kaur,
S.Yadav,
R.Krauspenhaar,
C.Betzel,
W.Voelter,
C.R.Babu,
and
T.P.Singh
(2005).
Crystal structure of himalayan mistletoe ribosome-inactivating protein reveals the presence of a natural inhibitor and a new functionally active sugar-binding site.
|
| |
J Biol Chem,
280,
20712-20721.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
Y.S.Youn,
D.H.Na,
S.D.Yoo,
S.C.Song,
and
K.C.Lee
(2005).
Carbohydrate-specifically polyethylene glycol-modified ricin A-chain with improved therapeutic potential.
|
| |
Int J Biochem Cell Biol,
37,
1525-1533.
|
|
|
|
|
|
|
C.A.McHugh,
R.F.Tammariello,
C.B.Millard,
and
J.H.Carra
(2004).
Improved stability of a protein vaccine through elimination of a partially unfolded state.
|
| |
Protein Sci,
13,
2736-2743.
|
|
|
|
|
|
|
C.J.Marsden,
V.Fülöp,
P.J.Day,
and
J.M.Lord
(2004).
The effect of mutations surrounding and within the active site on the catalytic activity of ricin A chain.
|
| |
Eur J Biochem,
271,
153-162.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
R.F.Fischetti,
D.J.Rodi,
D.B.Gore,
and
L.Makowski
(2004).
Wide-angle X-ray solution scattering as a probe of ligand-induced conformational changes in proteins.
|
| |
Chem Biol,
11,
1431-1443.
|
|
|
|
|
|
|
D.C.Smith,
C.J.Marsden,
J.M.Lord,
and
L.M.Roberts
(2003).
Expression, Purification and Characterization of Ricin vectors used for exogenous antigen delivery into the MHC Class I presentation pathway.
|
| |
Biol Proced Online,
5,
13-19.
|
|
|
|
|
|
|
M.A.Olson
(2001).
Electrostatic effects on the free-energy balance in folding a ribosome-inactivating protein.
|
| |
Biophys Chem,
91,
219-229.
|
|
|
|
|
|
|
J.R.Hesselberth,
D.Miller,
J.Robertus,
and
A.D.Ellington
(2000).
In vitro selection of RNA molecules that inhibit the activity of ricin A-chain.
|
| |
J Biol Chem,
275,
4937-4942.
|
|
|
|
|
|
|
J.Wesche,
A.Rapak,
and
S.Olsnes
(1999).
Dependence of ricin toxicity on translocation of the toxin A-chain from the endoplasmic reticulum to the cytosol.
|
| |
J Biol Chem,
274,
34443-34449.
|
|
|
|
|
|
|
M.A.Olson,
and
L.Cuff
(1999).
Free energy determinants of binding the rRNA substrate and small ligands to ricin A-chain.
|
| |
Biophys J,
76,
28-39.
|
|
|
|
|
|
|
J.K.Suh,
C.J.Hovde,
and
J.D.Robertus
(1998).
Shiga toxin attacks bacterial ribosomes as effectively as eucaryotic ribosomes.
|
| |
Biochemistry,
37,
9394-9398.
|
|
|
|
|
|
|
X.Y.Chen,
T.M.Link,
and
V.L.Schramm
(1998).
Ricin A-chain: kinetics, mechanism, and RNA stem-loop inhibitors.
|
| |
Biochemistry,
37,
11605-11613.
|
|
|
|
|
|
|
V.L.Schramm
(1997).
Enzymatic N-riboside scission in RNA and RNA precursors.
|
| |
Curr Opin Chem Biol,
1,
323-331.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
|
|
Links
