5EW2

Human thrombin sandwiched between two DNA aptamers: HD22 and HD1-deltaT12

Summary for 5EW2

• Entry DOI: 10.2210/pdb5ew2/pdb
• Related PRD ID: PRD_000020
• Descriptor: thrombin light chain, Thrombin heavy chain, HD22 (27mer), ... (8 entities in total)
• Functional Keywords: protein-dna complex, blood coagulation, dna aptamer, dna-inhibitor, g-quadruplex, duplex-quadruplex junction, serine protease, hydrolase, abasic furan, hydrolase-dna complex, protein/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 47725.30

Authors

Pica, A.,Russo Krauss, I.,Parente, V.,Sica, F. (deposition date: 2015-11-20, release date: 2016-11-30, Last modification date: 2024-10-16)

Primary citation

Pica, A.,Russo Krauss, I.,Parente, V.,Tateishi-Karimata, H.,Nagatoishi, S.,Tsumoto, K.,Sugimoto, N.,Sica, F.
Through-bond effects in the ternary complexes of thrombin sandwiched by two DNA aptamers.
Nucleic Acids Res., 45:461-469, 2017

PubMed Abstract: Aptamers directed against human thrombin can selectively bind to two different exosites on the protein surface. The simultaneous use of two DNA aptamers, HD1 and HD22, directed to exosite I and exosite II respectively, is a very powerful approach to exploit their combined affinity. Indeed, strategies to link HD1 and HD22 together have been proposed in order to create a single bivalent molecule with an enhanced ability to control thrombin activity. In this work, the crystal structures of two ternary complexes, in which thrombin is sandwiched between two DNA aptamers, are presented and discussed. The structures shed light on the cross talk between the two exosites. The through-bond effects are particularly evident at exosite II, with net consequences on the HD22 structure. Moreover, thermodynamic data on the binding of the two aptamers are also reported and analyzed.

PubMed: 27899589
DOI: 10.1093/nar/gkw1113

Experimental method

X-RAY DIFFRACTION (3.59 Å)