PDBsum entry 1rnf

Hydrolase

PDB id: 1rnf

Contents

Protein chains

120 a.a. *

Waters ×117

* Residue conservation analysis

PDB id:

1rnf

Name:

Hydrolase

Title:

X-ray crystal structure of unliganded human ribonuclease 4

Structure:

Protein (ribonuclease 4). Chain: a, b. Synonym: rnase 4. Engineered: yes

Source:

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

Resolution:

2.10Å R-factor: 0.174 R-free: 0.236

Authors:

S.S.Terzyan,R.Peracaula,R.De Llorens,Y.Tsushima,H.Yamada,M.Seno, F.X.Gomis-Rueth,M.Coll

Key ref:

S.S.Terzyan et al. (1999). The three-dimensional structure of human RNase 4, unliganded and complexed with d(Up), reveals the basis for its uridine selectivity. J Mol Biol, 285, 205-214. PubMed id: 9878400 DOI: 10.1006/jmbi.1998.2288

Date:

29-Oct-98 Release date: 29-Oct-99

Protein chains

P34096  (RNAS4_HUMAN) -  Ribonuclease 4 from Homo sapiens

Seq: 147 a.a.

Struc: 120 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.3.1.27.- - ?????

DOI no: 10.1006/jmbi.1998.2288

J Mol Biol 285:205-214 (1999)

PubMed id: 9878400

The three-dimensional structure of human RNase 4, unliganded and complexed with d(Up), reveals the basis for its uridine selectivity.

S.S.Terzyan, R.Peracaula, R.de Llorens, Y.Tsushima, H.Yamada, M.Seno, F.X.Gomis-Rüth, M.Coll.

ABSTRACT

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.

Selected figure(s)

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].

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.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 285, 205-214) copyright 1999.

Figures were selected by the author.