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PDBsum entry 1o2a
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Functional analysis of substrate and cofactor complex structures of a thymidylate synthase-Complementing protein.
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Authors
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I.I.Mathews,
A.M.Deacon,
J.M.Canaves,
D.Mcmullan,
S.A.Lesley,
S.Agarwalla,
P.Kuhn.
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Ref.
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Structure, 2003,
11,
677-690.
[DOI no: ]
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PubMed id
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Abstract
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Like thymidylate synthase (TS) in eukaryotes, the thymidylate
synthase-complementing proteins (TSCPs) are mandatory for cell survival of many
prokaryotes in the absence of external sources of thymidylate. Details of the
mechanism of this novel family of enzymes are unknown. Here, we report the
structural and functional analysis of a TSCP from Thermotoga maritima and its
complexes with substrate, analogs, and cofactor. The structures presented here
provide a basis for rationalizing the TSCP catalysis and reveal the possibility
of the design of an inhibitor. We have identified a new helix-loop-strand FAD
binding motif characteristic of the enzymes in the TSCP family. The presence of
a hydrophobic core with residues conserved among the TSCP family suggests a
common overall fold.
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Figure 2.
Figure 2. Structure of TM0449(A) View of the monomer.(B)
Topology diagram of the monomer (Westhead et al., 1998). b
strands, filled black triangles; a helices, filled blue circles.
Strand directions are indicated using upward-pointing or
downward-pointing triangles. N and C termini are labeled.(C)
View of the monomer orthogonal to the view in (A).(D) View of
the tetramer showing bound FAD molecules. Flavin ring exposed to
the surface in one of the monomers is shown with an arrow.(E)
Orthogonal view of the tetramer. The paired FAD molecules on
each side of the tetramer, cyan and black.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2003,
11,
677-690)
copyright 2003.
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