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PDBsum entry 2nxq
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Metal binding protein
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PDB id
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2nxq
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References listed in PDB file
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Key reference
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Title
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Crystal structure of calcium binding protein-1 from entamoeba histolytica: a novel arrangement of ef hand motifs.
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Authors
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S.Kumar,
N.Padhan,
N.Alam,
S.Gourinath.
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Ref.
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Proteins, 2007,
68,
990-998.
[DOI no: ]
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PubMed id
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Abstract
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Calcium plays a pivotal role in the pathogenesis of amoebiasis, a major disease
caused by Entamoeba histolytica. Several EF-hand containing calcium-binding
proteins (CaBPs) have been identified from E. histolytica. Even though these
proteins have very high sequence similarity, they bind to different target
proteins in a Ca2+ dependent manner, leading to different functional pathways
(Yadava et al., Mol Biochem Parasito 1997;84:69-82; Chakrabarty et al., J Biol
Chem 2004;279:12898-12908) The crystal structure of the Entamoeba histolytica
calcium binding protein-1 (EhCaBP1) has been determined at 2.4 A resolution. The
crystals were grown using MPD as precipitant and they belong to P6(3) space
group with unit cell parameters of a = 95.25 A, b = 95.25 A, c = 64.99 A. Only
two out of the four expected EF hand motifs could be modeled into the electron
density map and the final model refined to R factor of 25.6% and Free_R of 28%.
Unlike CaM, the first two EF hand motifs in EhCaBP1 are connected by a long
helix and form a dumbbell shaped structure. Owing to domain swapping
oligomerization three EhCaBP1 molecules interact in a head to tail manner to
form a triangular trimer. This arrangement allows the EF-hand motif of one
molecule to interact with that of an adjacent molecule to form a two EF-hand
domain similar to that seen in the N-terminal domain of the NMR structure of
CaBP1, calmodulin and troponin C. The oligomeric state of EhCaBP1 results in
reduced flexibility between domains and may be responsible for the more limited
set of targets recognized by EhCaBP1.
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Figure 1.
Figure 1. Structure of Calcium binding protein 1 from E.
histolytica (EhCaBP1). (A) Schematic representation of CaBP1,
showing calcium binding loops (CaBL) with residue numbers (CaBL1
in blue and CaBL2 in red). The central linker region of the
protein is displayed in orange, which has three glycines
imparting flexibility to the molecule. (B) Structure of
N-terminal half of the CaBP1 traced in the crystal structure is
displayed as a ribbon diagram generated by PyMOL,[25] calcium's
(grey) are shown as spheres in two EF hand motifs. Two EF hand
motifs are connected by straight helix (green). (C) Connecting
helix between two EF hand motifs is well defined. Part of the
helix is shown with 2Fo-Fc electron density map at 2  .
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Figure 5.
Figure 5. A superposition of CaM on trimer of EhCaBP1 that
reveals the similarity of the assembled domain to CaM N-terminal
domain. (A) The CaM N-terminal domain (red) was superposed (by
least square fit) on assembled domain of EF1 of one molecule
(light blue) and EF2 of neighboring molecule (purple) highlights
the domain similarity. The distance between N-terminal and
C-terminal domains in CaM is approximately equal to the distance
between the two assembled domains of EhCaBP1 trimer. But the
linker helix in CaM bends about 15° and thus C-terminal
domain of CaM do not overlap with the next assembled domain.
(B). Magnified view of CaM N-terminal domain (red) superposed on
assembled domain of EhCaBP1 trimer (EF1 in blue, EF2 in purple).
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2007,
68,
990-998)
copyright 2007.
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