PDBsum entry 2vq9

Hydrolase

PDB id: 2vq9

Contents

Protein chain

123 a.a. *

Metals

_CL ×2

Waters ×85

* Residue conservation analysis

PDB id:

2vq9

Name:

Hydrolase

Title:

Rnase zf-3e

Structure:

Rnase 1. Chain: a. Fragment: residues 23-149. Synonym: rnase zf-3e. Engineered: yes

Source:

Danio rerio. Zebrafish. Organism_taxid: 7955. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.85Å R-factor: 0.200 R-free: 0.254

Authors:

K.Kazakou,D.E.Holloway,S.H.Prior,V.Subramanian,K.R.Acharya

Key ref:

K.Kazakou et al. (2008). Ribonuclease A homologues of the zebrafish: polymorphism, crystal structures of two representatives and their evolutionary implications. J Mol Biol, 380, 206-222. PubMed id: 18508078 DOI: 10.1016/j.jmb.2008.04.070

Date:

12-Mar-08 Release date: 17-Jun-08

Protein chain

A5HAK0  (RNSL3_DANRE) -  Ribonuclease-like 3 from Danio rerio

Seq: 149 a.a.

Struc: 123 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.27.- - ?????

DOI no: 10.1016/j.jmb.2008.04.070

J Mol Biol 380:206-222 (2008)

PubMed id: 18508078

Ribonuclease A homologues of the zebrafish: polymorphism, crystal structures of two representatives and their evolutionary implications.

K.Kazakou, D.E.Holloway, S.H.Prior, V.Subramanian, K.R.Acharya.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 380, 206-222) copyright 2008.

Figures were selected by an automated process.