PDBsum entry 1wdy

Hydrolase

PDB id: 1wdy

Contents

Protein chain

285 a.a. *

Ligands

25A

Waters ×220

* Residue conservation analysis

PDB id:

1wdy

Name:

Hydrolase

Title:

Crystal structure of ribonuclease

Structure:

2-5a-dependent ribonuclease. Chain: a. Fragment: residues 21-305. Synonym: 2-5a-dependent rnase, ribonuclease l, rnase l, ribonuclease 4. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.80Å R-factor: 0.203 R-free: 0.230

Authors:

N.Tanaka,M.Nakanishi,Y.Kusakabe,Y.Goto,Y.Kitade,K.T.Nakamura

Key ref:

N.Tanaka et al. (2004). Structural basis for recognition of 2',5'-linked oligoadenylates by human ribonuclease L. EMBO J, 23, 3929-3938. PubMed id: 15385955 DOI: 10.1038/sj.emboj.7600420

Date:

19-May-04 Release date: 05-Oct-04

Protein chain

Q05823  (RN5A_HUMAN) -  2-5A-dependent ribonuclease from Homo sapiens

Seq: 741 a.a.

Struc: 285 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.1.26.- - ?????

DOI no: 10.1038/sj.emboj.7600420

EMBO J 23:3929-3938 (2004)

PubMed id: 15385955

Structural basis for recognition of 2',5'-linked oligoadenylates by human ribonuclease L.

N.Tanaka, M.Nakanishi, Y.Kusakabe, Y.Goto, Y.Kitade, K.T.Nakamura.

ABSTRACT

An interferon-induced endoribonuclease, ribonuclease L (RNase L), is implicated in both the molecular mechanism of action of interferon and the fundamental control of RNA stability in mammalian cells. RNase L is catalytically active only after binding to an unusual activator molecule containing a 5'-phosphorylated 2',5'-linked oligoadenylate (2-5A), in the N-terminal half. Here, we report the crystal structure of the N-terminal ankyrin repeat domain (ANK) of human RNase L complexed with the activator 2-5A. This is the first structural view of an ankyrin repeat structure directly interacting with a nucleic acid, rather than with a protein. The ANK domain folds into eight ankyrin repeat elements and forms an extended curved structure with a concave surface. The 2-5A molecule is accommodated at a concave site and directly interacts with ankyrin repeats 2-4. Interestingly, two structurally equivalent 2-5A binding motifs are found at repeats 2 and 4. The structural basis for 2-5A recognition by ANK is essential for designing stable 2-5As with a high likelihood of activating RNase L.

Selected figure(s)

Figure 1.
Figure 1 Crystal structure of ANK complexed with 2-5A. (A) Structural and functional domains of RNase L. Ankyrin repeats are shown starting with blue at repeat 1 and ending with red at repeat 8. (B) Structure of the predominant trimeric species of 2-5A ((pp)p(A2'p5')[2]A) (Kerr and Brown, 1978). (C, D) Surface (top) and ribbon (bottom) representations of the ANK/2-5A complex. Ankyrin repeats (R1 -R8) are shown as in (A). The bound 2-5A molecule is shown as a ball-and-stick model. The view in (D) was obtained by rotating the view in (C) by 90°.

Figure 3.
Figure 3 Recognition of 2-5A by ANK. (A) Stereodiagram showing the mode of 2-5A binding to ANK. The carbon atoms of ANK are colored as in Figure 1, and those of the bound 2-5A molecule are shown in white. Possible hydrogen bonds or salt bridges are indicated by dashed lines, and distances (in Å) are given. The refined model is superimposed on the weighted 2|F[o]| -|F[c]| map (1.5 , yellow) and the |F[o]| -|F[c]| omit map of 2-5A (4.5 , orange), calculated at 1.8 Å resolution. Bound water molecules are shown as spheres (cyan). (B, C) Recognition of the first and third AMP moieties of 2-5A by repeats 4 and 2, respectively, of ANK.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2004, 23, 3929-3938) copyright 2004.

Figures were selected by the author.