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PDBsum entry 2vq9
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References listed in PDB file
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Key reference
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Title
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Ribonuclease a homologues of the zebrafish: polymorphism, Crystal structures of two representatives and their evolutionary implications.
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Authors
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K.Kazakou,
D.E.Holloway,
S.H.Prior,
V.Subramanian,
K.R.Acharya.
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Ref.
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J Mol Biol, 2008,
380,
206-222.
[DOI no: ]
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PubMed id
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Abstract
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The widespread and functionally varied members of the ribonuclease A (RNase A)
superfamily provide an excellent opportunity to study evolutionary forces at
work on a conserved protein scaffold. Representatives from the zebrafish are of
particular interest as the evolutionary distance from non-ichthyic homologues is
large. We conducted an exhaustive survey of available zebrafish DNA sequences
and found significant polymorphism among its four known homologues. In an
extension of previous nomenclature, the variants have been named RNases
ZF-1a-c,-2a-d,-3a-e and-4. We present the first X-ray crystal structures of
zebrafish ribonucleases, RNases ZF-1a and-3e at 1.35-and 1.85 A resolution,
respectively. Structure-based clustering with ten other ribonuclease structures
indicates greatest similarity to mammalian angiogenins and amphibian
ribonucleases, and supports the view that all present-day ribonucleases evolved
from a progenitor with three disulphide bonds. In their details, the two
structures are intriguing melting-pots of features present in ribonucleases from
other vertebrate classes. Whereas in RNase ZF-1a the active site is obstructed
by the C-terminal segment (as observed in angiogenin), in RNase ZF-3e the same
region is open (as observed in more catalytically efficient homologues). The
progenitor of present-day ribonucleases is more likely to have had an
obstructive C terminus, and the relatively high similarity (late divergence) of
RNases ZF-1 and-3 infers that the active site unblocking event has happened
independently in different vertebrate lineages.
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Figure 1.
Fig. 1. Alignment of the sequences of zebrafish RNase
variants. Sequences were deduced from the sources given in Table
1 (nucleic acids encoding RNases ZF-1a–c,-2b–2d,-3d and-3e
were resequenced during the course of this work). Residues
predicted to form the signal peptide and mature chain of each
protein are written in grey and black text, respectively.
Residues conserved throughout are shaded blue, while those that
vary within each subclass are shaded gold. Likely members of the
catalytic triad are denoted by asterisks.
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Figure 5.
Fig. 5. Structural relationships among ribonucleases. C^α
coordinates of RNase ZF-1a, RNase ZF-3e, mAng-4 (PDB entry 2J4T,
chain A),^30 hAng (PDB entry 1B1I),^21 RNase A·d(CpA)
(PDB entry 1RPG),^22 hRNase 4 (PDB entry 1RNF, chain A),^37
hECP·2′,5′-ADP (PDB entry 1H1H),^24 hEDN (PDB entry
1GQV),^23 hRNase 7 (PDB entry 2HKY, model no. 15),^25
RC-RNase·d(ACGA) (PDB entry 1M07, chain A),^27 Amph-2
(PDB entry 2P7S)^28 and ONC (PDB entry 1ONC)^26 were aligned
with CE-MC,^82 and a loop-based Hausdorff measure (LHM) of
structural dissimilarity^31 was used to compute a pairwise
distance matrix. A clustering tree was then constructed using
the UNJ method,^83 and rooted by reference to the fossil
record.^85 Branch lengths are scaled according to LHM distance;
measured and reconstructed distances differ by 0.23 Å
(mean) and peak at 0.66 Å (RNase ZF-3 versus RNase 7).
Proteins with similar disulphide-bonding patterns are bracketed
(the subscripted letters denote alternative 4 × (S–S)
arrangements), while those that have obstructed B[1] subsites
and are angiogenic are marked with a red circle. Ichthyic,
mammalian and amphibian clades are coloured blue, black and
green, respectively.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2008,
380,
206-222)
copyright 2008.
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