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PDBsum entry 2csd
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References listed in PDB file
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Key reference
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Title
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Structure of the n-Terminal fragment of topoisomerase V reveals a new family of topoisomerases.
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Authors
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B.Taneja,
A.Patel,
A.Slesarev,
A.Mondragón.
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Ref.
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EMBO J, 2006,
25,
398-408.
[DOI no: ]
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PubMed id
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Abstract
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Topoisomerases are involved in controlling and maintaining the topology of DNA
and are present in all kingdoms of life. Unlike all other types of
topoisomerases, similar type IB enzymes have only been identified in bacteria
and eukarya. The only putative type IB topoisomerase in archaea is represented
by Methanopyrus kandleri topoisomerase V. Despite several common functional
characteristics, topoisomerase V shows no sequence similarity to other members
of the same type. The structure of the 61 kDa N-terminal fragment of
topoisomerase V reveals no structural similarity to other topoisomerases.
Furthermore, the structure of the active site region is different, suggesting no
conservation in the cleavage and religation mechanism. Additionally, the active
site is buried, indicating the need of a conformational change for activity. The
presence of a topoisomerase in archaea with a unique structure suggests the
evolution of a separate mechanism to alter DNA.
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Figure 2.
Figure 2 The multiHhH domain is flexible, while the
topoisomerase domain is rigid. Schematic diagram showing the
superposition of the two monomers in the asymmetric unit of
crystal Form I. The active site residues are shown in yellow. In
(A) only the multiHhH domains were used for the superposition,
while in (B) the topoisomerase domains were used for the
superposition. The figure illustrates the variability in the
multiHhH domains (Supplementary data). For clarity, in each
monomer the topoisomerase domain and the multiHhH domain are
shown in different shades of the same color.
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Figure 4.
Figure 4 Model for a topoisomerase domain-DNA complex. (A)
Electrostatic surface representation of the topoisomerase
domain. The diagram shows that the topoisomerase has a large
positively charged groove in one face of the protein centered
around the active site. The insets correspond to 90° views of
the molecule and show that there are no additional large
positively charged regions in the protein. The electrostatic
potential was calculated with the program APBS (Baker et al,
2001), with a dielectric constant of 80 for the solvent and 20
for the protein. The surface is colored with a blue to red
gradient from +5 to -5 K[b]T/e. (B) The diagram shows a model of
the topoisomerase domain in complex with B-DNA. The coloring
scheme is the same as in Figure 1. To create the model, the
linker helix and the multiHhH domain were removed. DNA was
docked using the HTH motif of human Pax6-paired domain-DNA
complex (Xu et al, 1999), but replacing the DNA with a
canonical, straight B-DNA model. No attempts were made to
prevent steric clashes. In the model, the active site tyrosine
is ideally placed to interact with the phosphodiester backbone
and the other putative active site residues are also in the
vicinity of DNA. The model suggests a potential way for topo-61
to interact with DNA, making extensive interactions.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
EMBO J
(2006,
25,
398-408)
copyright 2006.
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