PDBsum entry 2rnf

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Hydrolase PDB id
Protein chains
120 a.a. *
UM3 ×2
Waters ×111
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: X-ray crystal structure of human ribonuclease 4 in complex with d(up)
Structure: 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
Biol. unit: Dimer (from PQS)
2.40Å     R-factor:   0.160     R-free:   0.215
Authors: S.S.Terzyan,R.Peracaula,R.De Llorens,Y.Tsushima,H.Yamada, M.Seno,F.X.Gomis-Ruth,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
03-Nov-98     Release date:   10-Nov-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P34096  (RNAS4_HUMAN) -  Ribonuclease 4
147 a.a.
120 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     cellular response to starvation   3 terms 
  Biochemical function     nucleic acid binding     5 terms  


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, Llorens, Y.Tsushima, H.Yamada, M.Seno, F.X.Gomis-Rüth, M.Coll.
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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20522487 C.H.Hsu, Y.R.Pan, Y.D.Liao, S.H.Wu, and C.Chen (2010).
NMR and biophysical elucidation of structural effects on extra N-terminal methionine residue of recombinant amphibian RNases from Rana catesbeiana.
  J Biochem, 148, 209-215.  
18508078 K.Kazakou, D.E.Holloway, S.H.Prior, V.Subramanian, and K.R.Acharya (2008).
Ribonuclease A homologues of the zebrafish: polymorphism, crystal structures of two representatives and their evolutionary implications.
  J Mol Biol, 380, 206-222.
PDB codes: 2vq8 2vq9
18673284 T.J.Rutkoski, and R.T.Raines (2008).
Evasion of ribonuclease inhibitor as a determinant of ribonuclease cytotoxicity.
  Curr Pharm Biotechnol, 9, 185-189.  
17586772 H.Yamada, T.Tamada, M.Kosaka, K.Miyata, S.Fujiki, M.Tano, M.Moriya, M.Yamanishi, E.Honjo, H.Tada, T.Ino, H.Yamaguchi, J.Futami, M.Seno, T.Nomoto, T.Hirata, M.Yoshimura, and R.Kuroki (2007).
'Crystal lattice engineering,' an approach to engineer protein crystal contacts by creating intermolecular symmetry: crystallization and structure determination of a mutant human RNase 1 with a hydrophobic interface of leucines.
  Protein Sci, 16, 1389-1397.
PDB codes: 2e0j 2e0l 2e0m 2e0o
16433931 H.T.Chang, T.W.Pai, T.C.Fan, B.H.Su, P.C.Wu, C.Y.Tang, C.T.Chang, S.H.Liu, and M.D.Chang (2006).
A reinforced merging methodology for mapping unique peptide motifs in members of protein families.
  BMC Bioinformatics, 7, 38.  
12954760 Y.D.Liao, S.C.Wang, Y.J.Leu, C.F.Wang, S.T.Chang, Y.T.Hong, Y.R.Pan, and C.Chen (2003).
The structural integrity exerted by N-terminal pyroglutamate is crucial for the cytotoxicity of frog ribonuclease from Rana pipiens.
  Nucleic Acids Res, 31, 5247-5255.  
12499382 Y.J.Leu, S.S.Chern, S.C.Wang, Y.Y.Hsiao, I.Amiraslanov, Y.C.Liaw, and Y.D.Liao (2003).
Residues involved in the catalysis, base specificity, and cytotoxicity of ribonuclease from Rana catesbeiana based upon mutagenesis and X-ray crystallography.
  J Biol Chem, 278, 7300-7309.
PDB code: 1m07
11264578 J.Pous, G.Mallorquí-Fernández, R.Peracaula, S.S.Terzyan, J.Futami, H.Tada, H.Yamada, M.Seno, Llorens, F.X.Gomis-Rüth, and M.Coll (2001).
Three-dimensional structure of human RNase 1 delta N7 at 1.9 A resolution.
  Acta Crystallogr D Biol Crystallogr, 57, 498-505.
PDB code: 1e21
10691987 E.Fernández-Salas, R.Peracaula, M.L.Frazier, and Llorens (2000).
Ribonucleases expressed by human pancreatic adenocarcinoma cell lines.
  Eur J Biochem, 267, 1484-1494.  
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