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Angiogenin PDB id
1h53
Jmol
Contents
Protein chain
121 a.a. *
Ligands
CIT
PO4
Waters ×47
* Residue conservation analysis
PDB id:
1h53
Name: Angiogenin
Title: Binding of phosphate and pyrophosphate ions at the active site of human angiogenin as revealed by x-ray crystallography
Structure: Angiogenin. Chain: a. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.0Å     R-factor:   0.198     R-free:   0.260
Authors: D.D.Leonidas,G.B.Chavali,A.M.Jardine,S.Li,R.Shapiro, K.R.Acharya
Key ref: D.D.Leonidas et al. (2001). Binding of phosphate and pyrophosphate ions at the active site of human angiogenin as revealed by X-ray crystallography. Protein Sci, 10, 1669-1676. PubMed id: 11468363 DOI: 10.1110/ps.13601
Date:
18-May-01     Release date:   09-Aug-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P03950  (ANGI_HUMAN) -  Angiogenin
Seq:
Struc: 		147 a.a.
121 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   8 terms 
  Biological process     metabolic process   24 terms 
  Biochemical function     nucleic acid binding     14 terms  

 

 
DOI no: 10.1110/ps.13601 Protein Sci 10:1669-1676 (2001)
PubMed id: 11468363  
 
 
Binding of phosphate and pyrophosphate ions at the active site of human angiogenin as revealed by X-ray crystallography.
D.D.Leonidas, G.B.Chavali, A.M.Jardine, S.Li, R.Shapiro, K.R.Acharya.
 
  ABSTRACT  
 
Human angiogenin (Ang) is an unusual homolog of bovine pancreatic RNase A that utilizes its ribonucleolytic activity to induce the formation of new blood vessels. The pyrimidine-binding site of Ang was shown previously to be blocked by glutamine 117, indicating that Ang must undergo a conformational change to bind and cleave RNA. The mechanism and nature of this change are not known, and no Ang-inhibitor complexes have been characterized structurally thus far. Here, we report crystal structures for the complexes of Ang with the inhibitors phosphate and pyrophosphate, and the structure of the complex of the superactive Ang variant Q117G with phosphate, all at 2.0 A resolution. Phosphate binds to the catalytic site of both Ang and Q117G in essentially the same manner observed in the RNase A-phosphate complex, forming hydrogen bonds with the side chains of His 13, His 114, and Gln 12, and the main chain of Leu 115; it makes an additional interaction with the Lys 40 ammonium group in the Ang complex. One of the phosphate groups of pyrophosphate occupies a similar position. The other phosphate extends toward Gln 117, and lies within hydrogen-bonding distance from the side-chain amide of this residue as well as the imidazole group of His 13 and the main-chain oxygen of Leu 115. The pyrimidine site remains obstructed in all three complex structures, that is, binding to the catalytic center is not sufficient to trigger the conformational change required for catalytic activity, even in the absence of the Gln 117 side chain. The Ang-pyrophosphate complex structure suggests how nucleoside pyrophosphate inhibitors might bind to Ang; this information may be useful for the design of Ang antagonists as potential anti-angiogenic drugs.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21050179 E.Pizzo, A.Merlino, M.Turano, I.Russo Krauss, F.Coscia, A.Zanfardino, M.Varcamonti, A.Furia, C.Giancola, L.Mazzarella, F.Sica, and G.D'Alessio (2010).
A new RNase sheds light on the RNase/angiogenin subfamily from zebrafish.
  Biochem J, 433, 345-355.
PDB codes: 3ljd 3lje 3ln8
19191310 D.E.Holloway, G.B.Chavali, D.D.Leonidas, M.D.Baker, and K.R.Acharya (2009).
Influence of naturally-occurring 5'-pyrophosphate-linked substituents on the binding of adenylic inhibitors to ribonuclease a: An X-ray crystallographic study.
  Biopolymers, 91, 995.
PDB codes: 2w5g 2w5i 2w5k 2w5l 2w5m
16301790 D.E.Holloway, G.B.Chavali, M.C.Hares, V.Subramanian, and K.R.Acharya (2005).
Structure of murine angiogenin: features of the substrate- and cell-binding regions and prospects for inhibitor-binding studies.
  Acta Crystallogr D Biol Crystallogr, 61, 1568-1578.
PDB codes: 2bwk 2bwl
12945053 A.Merlino, L.Vitagliano, M.A.Ceruso, and L.Mazzarella (2003).
Subtle functional collective motions in pancreatic-like ribonucleases: from ribonuclease A to angiogenin.
  Proteins, 53, 101-110.  
14573867 D.D.Leonidas, G.B.Chavali, N.G.Oikonomakos, E.D.Chrysina, M.N.Kosmopoulou, M.Vlassi, C.Frankling, and K.R.Acharya (2003).
High-resolution crystal structures of ribonuclease A complexed with adenylic and uridylic nucleotide inhibitors. Implications for structure-based design of ribonucleolytic inhibitors.
  Protein Sci, 12, 2559-2574.
PDB codes: 1o0f 1o0h 1o0m 1o0n 1o0o
12471601 J.L.Jenkins, R.Y.Kao, and R.Shapiro (2003).
Virtual screening to enrich hit lists from high-throughput screening: a case study on small-molecule inhibitors of angiogenin.
  Proteins, 50, 81-93.  
12118120 R.Y.Kao, J.L.Jenkins, K.A.Olson, M.E.Key, J.W.Fett, and R.Shapiro (2002).
A small-molecule inhibitor of the ribonucleolytic activity of human angiogenin that possesses antitumor activity.
  Proc Natl Acad Sci U S A, 99, 10066-10071.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.