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PDBsum entry 3dd2
Go to PDB code: 
protein dna_rna ligands metals Protein-protein interface(s) links
Hydrolase/hydrolase inhibitor/RNA PDB id
3dd2

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
30 a.a. *
258 a.a. *
DNA/RNA
Ligands
PEG ×3
0G6
P6G
ACY ×6
Metals
_MG ×2
Waters ×253
* Residue conservation analysis
PDB id:
3dd2
Name: Hydrolase/hydrolase inhibitor/RNA
Title: Crystal structure of an RNA aptamer bound to human thrombin
Structure: Thrombin light chain. Chain: l. Thrombin heavy chain. Chain: h. RNA (26-mer). Chain: b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Synthetic: yes
Resolution:
1.90Å     R-factor:   0.204     R-free:   0.254
Authors: S.B.Long,B.A.Sullenger
Key ref: S.B.Long et al. (2008). Crystal structure of an RNA aptamer bound to thrombin. Rna, 14, 2504-2512. PubMed id: 18971322
Date:
04-Jun-08     Release date:   11-Nov-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		622 a.a.
30 a.a.
Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		622 a.a.
258 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

DNA/RNA chain
  G-G-G-A-A-CFL-A-A-A-G-CFL-UFT-G-A-A-G-UFT-A-CFL-UFT-UFT-A-CFL-CFL-CFL-T 26 bases

 Enzyme reactions 
   Enzyme class: Chains L, H: E.C.3.4.21.5  - thrombin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.

 

 
Rna 14:2504-2512 (2008)
PubMed id: 18971322  
 
 
Crystal structure of an RNA aptamer bound to thrombin.
S.B.Long, M.B.Long, R.R.White, B.A.Sullenger.
 
  ABSTRACT  
 
Aptamers, an emerging class of therapeutics, are DNA or RNA molecules that are selected to bind molecular targets that range from small organic compounds to large proteins. All of the determined structures of aptamers in complex with small molecule targets show that aptamers cage such ligands. In structures of aptamers in complex with proteins that naturally bind nucleic acid, the aptamers occupy the nucleic acid binding site and often mimic the natural interactions. Here we present a crystal structure of an RNA aptamer bound to human thrombin, a protein that does not naturally bind nucleic acid, at 1.9 A resolution. The aptamer, which adheres to thrombin at the binding site for heparin, presents an extended molecular surface that is complementary to the protein. Protein recognition involves the stacking of single-stranded adenine bases at the core of the tertiary fold with arginine side chains. These results exemplify how RNA aptamers can fold into intricate conformations that allow them to interact closely with extended surfaces on non-RNA binding proteins.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20213669 M.Torrent, M.V.Nogués, and E.Boix (2011).
Eosinophil cationic protein (ECP) can bind heparin and other glycosaminoglycans through its RNase active site.
  J Mol Recognit, 24, 90.  
21080818 E.N.Brody, L.Gold, R.M.Lawn, J.J.Walker, and D.Zichi (2010).
High-content affinity-based proteomics: unlocking protein biomarker discovery.
  Expert Rev Mol Diagn, 10, 1013-1022.  
20007153 M.C.Buff, F.Schäfer, B.Wulffen, J.Müller, B.Pötzsch, A.Heckel, and G.Mayer (2010).
Dependence of aptamer activity on opposed terminal extensions: improvement of light-regulation efficiency.
  Nucleic Acids Res, 38, 2111-2118.  
20348921 N.Clementi, A.Chirkova, B.Puffer, R.Micura, and N.Polacek (2010).
Atomic mutagenesis reveals A2660 of 23S ribosomal RNA as key to EF-G GTPase activation.
  Nat Chem Biol, 6, 344-351.  
20022942 S.K.Buddai, J.M.Layzer, G.Lu, C.P.Rusconi, B.A.Sullenger, D.M.Monroe, and S.Krishnaswamy (2010).
An anticoagulant RNA aptamer that inhibits proteinase-cofactor interactions within prothrombinase.
  J Biol Chem, 285, 5212-5223.  
21080135 T.J.Povsic, B.A.Sullenger, S.L.Zelenkofske, C.P.Rusconi, and R.C.Becker (2010).
Translating nucleic acid aptamers to antithrombotic drugs in cardiovascular medicine.
  J Cardiovasc Transl Res, 3, 704-716.  
20675355 Y.Nomura, S.Sugiyama, T.Sakamoto, S.Miyakawa, H.Adachi, K.Takano, S.Murakami, T.Inoue, Y.Mori, Y.Nakamura, and H.Matsumura (2010).
Conformational plasticity of RNA for target recognition as revealed by the 2.15 A crystal structure of a human IgG-aptamer complex.
  Nucleic Acids Res, 38, 7822-7829.
PDB code: 3agv
19589779 N.S.Petrera, A.R.Stafford, B.A.Leslie, C.A.Kretz, J.C.Fredenburgh, and J.I.Weitz (2009).
Long range communication between exosites 1 and 2 modulates thrombin function.
  J Biol Chem, 284, 25620-25629.  
19913482 R.H.Huang, D.H.Fremont, J.L.Diener, R.G.Schaub, and J.E.Sadler (2009).
A structural explanation for the antithrombotic activity of ARC1172, a DNA aptamer that binds von Willebrand factor domain A1.
  Structure, 17, 1476-1484.
PDB codes: 3hxo 3hxq
19846574 S.M.Nimjee, S.Oney, Z.Volovyk, K.M.Bompiani, S.B.Long, M.Hoffman, and B.A.Sullenger (2009).
Synergistic effect of aptamers that inhibit exosites 1 and 2 on thrombin.
  RNA, 15, 2105-2111.  
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 code is shown on the right.

 

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