Summary information [schematics · tetrads · helices · stems · costacks · homepage]

PDB-id
4lz4
Class
hydrolase-hydrolase inhibitor-DNA
Method
X-ray (2.56 Å)
Summary
X-ray structure of the complex between human thrombin and the tba deletion mutant lacking thymine 3 nucleobase
Reference
Pica, A., Russo Krauss, I., Merlino, A., Nagatoishi, S., Sugimoto, N., Sica, F.: (2013) "Dissecting the contribution of thrombin exosite I in the recognition of thrombin binding aptamer." Febs J., 280, 6581-6588.
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.
G4 notes
4 G-tetrads, 2 G4 helices, 2 G4 stems · 2(+Ln+Lw+Ln), chair(2+2), UDUD

Base-block schematics in six views [summary · tetrads · helices · stems · costacks · homepage]

PyMOL session file PDB file View in 3Dmol.js

List of 4 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 1 glyco-bond=s-s- groove=wnwn planarity=0.431 type=other  nts=4 GGGG E.DG1,E.DG15,E.DG10,E.DG6
 2 glyco-bond=-s-s groove=wnwn planarity=0.477 type=bowl-2 nts=4 GGGG E.DG2,E.DG14,E.DG11,E.DG5
 3 glyco-bond=s-s- groove=wnwn planarity=0.447 type=other  nts=4 GGGG F.DG1,F.DG15,F.DG10,F.DG6
 4 glyco-bond=-s-s groove=wnwn planarity=0.428 type=bowl-2 nts=4 GGGG F.DG2,F.DG14,F.DG11,F.DG5

List of 2 G4-helices [summary · schematics · tetrads · stems · costacks · homepage]

In DSSR, a G4-helix is defined by stacking interactions of G-tetrads, regardless of backbone connectivity, and may contain more than one G4-stem.

Helix#1, 2 G-tetrad layers, INTRA-molecular, with 1 stem

 1  glyco-bond=s-s- groove=wnwn Major-->WC nts=4 GGGG E.DG1,E.DG15,E.DG10,E.DG6
 2  glyco-bond=-s-s groove=wnwn WC-->Major nts=4 GGGG E.DG2,E.DG14,E.DG11,E.DG5
  step#1  mm(<>,outward)  area=19.78 rise=3.52 twist=13.4
  strand#1 DNA glyco-bond=s- nts=2 GG E.DG1,E.DG2
  strand#2 DNA glyco-bond=-s nts=2 GG E.DG15,E.DG14
  strand#3 DNA glyco-bond=s- nts=2 GG E.DG10,E.DG11
  strand#4 DNA glyco-bond=-s nts=2 GG E.DG6,E.DG5

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1 stacking diagram
 1  glyco-bond=s-s- groove=wnwn Major-->WC nts=4 GGGG E.DG1,E.DG15,E.DG10,E.DG6
2 glyco-bond=-s-s groove=wnwn WC-->Major nts=4 GGGG E.DG2,E.DG14,E.DG11,E.DG5
step#1 mm(<>,outward) area=19.78 rise=3.52 twist=13.4

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Helix#2, 2 G-tetrad layers, INTRA-molecular, with 1 stem

 1  glyco-bond=s-s- groove=wnwn Major-->WC nts=4 GGGG F.DG1,F.DG15,F.DG10,F.DG6
 2  glyco-bond=-s-s groove=wnwn WC-->Major nts=4 GGGG F.DG2,F.DG14,F.DG11,F.DG5
  step#1  mm(<>,outward)  area=19.34 rise=3.53 twist=12.7
  strand#1 DNA glyco-bond=s- nts=2 GG F.DG1,F.DG2
  strand#2 DNA glyco-bond=-s nts=2 GG F.DG15,F.DG14
  strand#3 DNA glyco-bond=s- nts=2 GG F.DG10,F.DG11
  strand#4 DNA glyco-bond=-s nts=2 GG F.DG6,F.DG5

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1 stacking diagram
 1  glyco-bond=s-s- groove=wnwn Major-->WC nts=4 GGGG F.DG1,F.DG15,F.DG10,F.DG6
2 glyco-bond=-s-s groove=wnwn WC-->Major nts=4 GGGG F.DG2,F.DG14,F.DG11,F.DG5
step#1 mm(<>,outward) area=19.34 rise=3.53 twist=12.7

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List of 2 G4-stems [summary · schematics · tetrads · helices · costacks · homepage]

In DSSR, a G4-stem is defined as a G4-helix with backbone connectivity. Bulges are also allowed along each of the four strands.

Stem#1, 2 G-tetrad layers, 3 loops, INTRA-molecular, UDUD, anti-parallel, 2(+Ln+Lw+Ln), chair(2+2)

 1  glyco-bond=s-s- groove=wnwn Major-->WC nts=4 GGGG E.DG1,E.DG15,E.DG10,E.DG6
 2  glyco-bond=-s-s groove=wnwn WC-->Major nts=4 GGGG E.DG2,E.DG14,E.DG11,E.DG5
  step#1  mm(<>,outward)  area=19.78 rise=3.52 twist=13.4
  strand#1  U DNA glyco-bond=s- nts=2 GG E.DG1,E.DG2
  strand#2  D DNA glyco-bond=-s nts=2 GG E.DG15,E.DG14
  strand#3  U DNA glyco-bond=s- nts=2 GG E.DG10,E.DG11
  strand#4  D DNA glyco-bond=-s nts=2 GG E.DG6,E.DG5
  loop#1 type=lateral   strands=[#1,#4] nts=2 ?T E.3DR3,E.DT4
  loop#2 type=lateral   strands=[#4,#3] nts=3 TGT E.DT7,E.DG8,E.DT9
  loop#3 type=lateral   strands=[#3,#2] nts=2 TT E.DT12,E.DT13

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Stem#2, 2 G-tetrad layers, 3 loops, INTRA-molecular, UDUD, anti-parallel, 2(+Ln+Lw+Ln), chair(2+2)

 1  glyco-bond=s-s- groove=wnwn Major-->WC nts=4 GGGG F.DG1,F.DG15,F.DG10,F.DG6
 2  glyco-bond=-s-s groove=wnwn WC-->Major nts=4 GGGG F.DG2,F.DG14,F.DG11,F.DG5
  step#1  mm(<>,outward)  area=19.34 rise=3.53 twist=12.7
  strand#1  U DNA glyco-bond=s- nts=2 GG F.DG1,F.DG2
  strand#2  D DNA glyco-bond=-s nts=2 GG F.DG15,F.DG14
  strand#3  U DNA glyco-bond=s- nts=2 GG F.DG10,F.DG11
  strand#4  D DNA glyco-bond=-s nts=2 GG F.DG6,F.DG5
  loop#1 type=lateral   strands=[#1,#4] nts=2 ?T F.3DR3,F.DT4
  loop#2 type=lateral   strands=[#4,#3] nts=3 TGT F.DT7,F.DG8,F.DT9
  loop#3 type=lateral   strands=[#3,#2] nts=2 TT F.DT12,F.DT13

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List of 0 G4 coaxial stacks [summary · schematics · tetrads · helices · stems · homepage]

List of 0 non-stem G4-loops (including the two closing Gs)