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PDBsum entry 1rnf
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The three-Dimensional structure of human rnase 4, Unliganded and complexed with d(up), Reveals the basis for its uridine selectivity.
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Authors
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S.S.Terzyan,
R.Peracaula,
R.De llorens,
Y.Tsushima,
H.Yamada,
M.Seno,
F.X.Gomis-Rüth,
M.Coll.
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Ref.
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J Mol Biol, 1999,
285,
205-214.
[DOI no: ]
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PubMed id
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Abstract
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The RNase 4 family is unique among RNase enzymes, displaying the highest level
of sequence similarity and encompassing the shortest polypeptide chain. It is
the only one showing high specificity. The human representative is an
intracellular and plasma enzyme, first isolated from colon adenocarcinoma cell
line HT-29. The crystal structures of human recombinant RNase 4, unliganded and
in complex with d(Up), have been determined, revealing in the unique active site
an explanation for the uridine specificity. Arg101, at a position not involved
in catalysis in the other RNase enzymes, penetrates the enzyme moiety shaping
the recognition pocket, a flip that is mediated by the interaction with the
(shorter chain) C-terminal carboxylate group, providing an anchoring point for
the O4 atom of the substrate uridine. The bulky Phe42 side-chain forces Asp80 to
be in the chi1=-72.49 degrees rotamer, accepting a hydrogen bond from Thr44,
further converting the latter into a hydrogen bond acceptor. This favours an
interaction with the -NH-donor group of uridine at position 3 over that with the
=N-acceptor of cytidine. The two chemical groups that distinguish uracyl from
cytosine are used by the enzyme to discriminate between these two bases.
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Figure 1.
Figure 1. Alignment of the amino acid sequences of human
RNases and bovine pancreatic RNase A. The α-helices and
β-strands of RNase 4 are displayed as labelled dark rods and
light arrows, respectively. The topologically equivalent
secondary structure elements in the enzymes with known
three-dimensional structures are shaded: α-helices with dark
grey background and β-strands with light grey. The upper
numbering corresponds to RNase 4 and the lower to RNase A.
Secondary structure elements in all of the structures have been
determined from their co-ordinates (PDB access code for RNase A
is 7RSA and for angiogenin 1ANG) using the program PROCHECK
[Laskowski et al 1993].
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Figure 2.
Figure 2. Schematic stereo representation of the RNase 4
polypeptide fold. The labelled helices (α1-α3), strands
(β1-β4) and loops are shown as helical ribbons, arrows and
thin tubes, respectively. The four disulphide bridges are shown
as white sticks. Labelling is according to Figure 1.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1999,
285,
205-214)
copyright 1999.
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