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PDBsum entry 1hap
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protein dna_rna ligands Protein-protein interface(s) links
Hydrolase/hydrolase inhibitor/DNA PDB id
1hap

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
27 a.a. *
253 a.a. *
DNA/RNA
Ligands
0G6
Waters ×151
* Residue conservation analysis
PDB id:
1hap
Name: Hydrolase/hydrolase inhibitor/DNA
Title: Complex of human alpha-thrombin with a 15mer oligonucleotide ggttggtgtggttgg (based on x-ray model of DNA)
Structure: 5'-d( Gp Gp Tp Tp Gp Gp Tp Gp Tp Gp Gp Tp Tp Gp G)-3'. Chain: d. Engineered: yes. Thrombin light chain. Chain: l. Fragment: residues 328-363. Synonym: coagulation factor ii. Thrombin heavy chain. Chain: h.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606
Biol. unit: Tetramer (from PQS)
Resolution:
2.80Å     R-factor:   0.161    
Authors: K.Padmanabhan,A.Tulinsky
Key ref:
K.Padmanabhan and A.Tulinsky (1996). An ambiguous structure of a DNA 15-mer thrombin complex. Acta Crystallogr D Biol Crystallogr, 52, 272-282. PubMed id: 15299700 DOI: 10.1107/S0907444995013977
Date:
03-Oct-95     Release date:   03-Apr-96    
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.
27 a.a.
Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		622 a.a.
253 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

DNA/RNA chain
  G-G-T-T-G-G-T-G-T-G-G-T-T-G-G 15 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.

 

 
DOI no: 10.1107/S0907444995013977 Acta Crystallogr D Biol Crystallogr 52:272-282 (1996)
PubMed id: 15299700  
 
 
An ambiguous structure of a DNA 15-mer thrombin complex.
K.Padmanabhan, A.Tulinsky.
 
  ABSTRACT  
 
The structure of a complex between thrombin and a GGTTGGTGTGGTTGG DNA 15-mer has been analyzed crystallographically. The solution NMR structure of the 15-mer has two stacked G-quartets similar to that found in the previous X-ray structure determination of the 15-mer-thrombin complex [Padmanabhan, Padmanabhan, Ferrara, Sadler & Tulinsky (1993). J. Biol. Chem. 268, 17651-17654]; the strand polarity, however, is reversed from that of the crystallographic structure. The structure of the complex here has been redetermined with better diffraction data confirming the previous crystallographic structure but also indicating that the NMR solution structure fits equally well. Both 15-mer complex structures refined to an R value of about 0.16 presenting a disconcerting ambiguity. Since the two 15-mer structures associate with thrombin in different ways (through the TGT loop in the X-ray and TT loop in the NMR model), other independent lines of physical or chemical evidence are required to resolve the ambiguity.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Schematic drawings of the X-ray (left) and NMR (right) structures of the aptamer. "IT loops span wide grooves, TGT spans narrow groove in X-ray structure and vice versa in NMR structure. 		Figure 7.
Fig. 7. Stereoview of the hydrophobic interaction sites of T3 and TI2 of the NMR model of the aptamer. The DNA is shown in thin lines and thrombin residues, which form the hydrophobic pockets located in the fibrinogen exosite at top (in bold). Heparin binding-site inter- actions at bottom (primed resi- dues). Only bases with good density shown.
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1996, 52, 272-282) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20369187 M.A.Ochsenkühn, and C.J.Campbell (2010).
Probing biomolecular interactions using surface enhanced Raman spectroscopy: label-free protein detection using a G-quadruplex DNA aptamer.
  Chem Commun (Camb), 46, 2799-2801.  
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.  
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.  
17890401 B.Pagano, L.Martino, A.Randazzo, and C.Giancola (2008).
Stability and binding properties of a modified thrombin binding aptamer.
  Biophys J, 94, 562-569.  
18971322 S.B.Long, M.B.Long, R.R.White, and B.A.Sullenger (2008).
Crystal structure of an RNA aptamer bound to thrombin.
  RNA, 14, 2504-2512.
PDB code: 3dd2
17891385 S.Balamurugan, A.Obubuafo, S.A.Soper, and D.A.Spivak (2008).
Surface immobilization methods for aptamer diagnostic applications.
  Anal Bioanal Chem, 390, 1009-1021.  
17636049 C.G.Peng, and M.J.Damha (2007).
G-quadruplex induced stabilization by 2'-deoxy-2'-fluoro-D-arabinonucleic acids (2'F-ANA).
  Nucleic Acids Res, 35, 4977-4988.  
16847867 C.Lin, E.Katilius, Y.Liu, J.Zhang, and H.Yan (2006).
Self-assembled signaling aptamer DNA arrays for protein detection.
  Angew Chem Int Ed Engl, 45, 5296-5301.  
16106044 J.Li, J.J.Correia, L.Wang, J.O.Trent, and J.B.Chaires (2005).
Not so crystal clear: the structure of the human telomere G-quadruplex in solution differs from that present in a crystal.
  Nucleic Acids Res, 33, 4649-4659.  
12573700 N.A.Raffler, J.Schneider-Mergener, and M.Famulok (2003).
A novel class of small functional peptides that bind and inhibit human alpha-thrombin isolated by mRNA display.
  Chem Biol, 10, 69-79.  
12682360 V.Dapić, V.Abdomerović, R.Marrington, J.Peberdy, A.Rodger, J.O.Trent, and P.J.Bates (2003).
Biophysical and biological properties of quadruplex oligodeoxyribonucleotides.
  Nucleic Acids Res, 31, 2097-2107.  
11891627 J.Sühnel (2001).
Beyond nucleic acid base pairs: from triads to heptads.
  Biopolymers, 61, 32-51.  
11745112 R.H.Shafer, and I.Smirnov (2000).
Biological aspects of DNA/RNA quadruplexes.
  Biopolymers, 56, 209-227.  
9675197 G.D.Strahan, M.A.Keniry, and R.H.Shafer (1998).
NMR structure refinement and dynamics of the K+-[d(G3T4G3)]2 quadruplex via particle mesh Ewald molecular dynamics simulations.
  Biophys J, 75, 968-981.  
8807893 J.Feigon, T.Dieckmann, and F.W.Smith (1996).
Aptamer structures from A to zeta.
  Chem Biol, 3, 611-617.  
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.

 

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