PDBsum entry 4lz4

Hydrolase/hydrolase inhibitor/DNA

PDB id: 4lz4

Contents

Protein chains

34 a.a.

258 a.a.

DNA/RNA

Ligands

NAG ×2

0G6 ×2

Metals

_NA ×2

__K ×2

Waters ×219

PDB id:

4lz4

Name:

Hydrolase/hydrolase inhibitor/DNA

Title:

X-ray structure of the complex between human thrombin and the tba deletion mutant lacking thymine 3 nucleobase

Structure:

Thrombin light chain. Chain: a, c. Synonym: coagulation factor ii, activation peptide fragment 1, activation peptide fragment 2, thrombin light chain. Thrombin heavy chain. Chain: b, d. Synonym: coagulation factor ii, activation peptide fragment 1, activation peptide fragment 2, thrombin heavy chain. Thrombin binding aptamer (tba).

Source:

Homo sapiens. Human. Organism_taxid: 9606. Synthetic: yes. Other_details: synthetic DNA

Resolution:

2.56Å R-factor: 0.171 R-free: 0.227

Authors:

A.Pica,I.Russo Krauss,A.Merlino,F.Sica

Key ref:

A.Pica et al. (2013). Dissecting the contribution of thrombin exosite I in the recognition of thrombin binding aptamer. Febs J, 280, 6581-6588. PubMed id: 24128303 DOI: 10.1111/febs.12561

Date:

31-Jul-13 Release date: 08-Jan-14

Protein chains

P00734  (THRB_HUMAN) -  Prothrombin from Homo sapiens

Seq: 622 a.a.

Struc: 34 a.a.

Protein chains

P00734  (THRB_HUMAN) -  Prothrombin from Homo sapiens

Seq: 622 a.a.

Struc: 258 a.a.

DNA/RNA chains

G-G-3DR-T-G-G-T-G-T-G-G-T-T-G-G 15 bases

G-G-3DR-T-G-G-T-G-T-G-G-T-T-G-G 15 bases

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.3.4.21.5 - thrombin.
• Reaction: Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.

DOI no: 10.1111/febs.12561

Febs J 280:6581-6588 (2013)

PubMed id: 24128303

Dissecting the contribution of thrombin exosite I in the recognition of thrombin binding aptamer.

A.Pica, I.Russo Krauss, A.Merlino, S.Nagatoishi, N.Sugimoto, F.Sica.

ABSTRACT

Thrombin plays a pivotal role in the coagulation cascade; therefore, it represents a primary target in the treatment of several blood diseases. The 15-mer DNA oligonucleotide 5'-GGTTGGTGTGGTTGG-3', known as thrombin binding aptamer (TBA), is a highly potent inhibitor of the enzyme. TBA folds as an antiparallel chair-like G-quadruplex structure, with two G-tetrads surrounded by two TT loops on one side and a TGT loop on the opposite side. Previous crystallographic studies have shown that TBA binds thrombin exosite I by its TT loops, T3T4 and T12T13. In order to get a better understanding of the thrombin-TBA interaction, we have undertaken a crystallographic characterization of the complexes between thrombin and two TBA mutants, TBAΔT3 and TBAΔT12, which lack the nucleobase of T3 and T12, respectively. The structural details of the two complexes show that exosite I is actually split into two regions, which contribute differently to TBA recognition. These results provide the basis for a more rational design of new aptamers with improved therapeutic action.