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PDBsum entry 2esc
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Signaling protein
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PDB id
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2esc
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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 a bovine secretory signalling glycoprotein (spc-40) at 2.1 angstrom resolution.
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Authors
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J.Kumar,
A.S.Ethayathulla,
D.B.Srivastava,
S.Sharma,
S.B.Singh,
A.Srinivasan,
M.P.Yadav,
T.P.Singh.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2006,
62,
953-963.
[DOI no: ]
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PubMed id
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Abstract
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A recently discovered new class of 40 kDa glycoproteins forms a major component
of the secretory proteins in the dry secretions of non-lactating animals. These
proteins are implicated as protective signalling factors that determine which
cells are to survive during the processes of drastic tissue remodelling. In
order to understand its role in the remodelling of mammary glands, the detailed
three-dimensional structure of the bovine signalling glycoprotein (SPC-40) has
been determined using X-ray crystallography. SPC-40 was purified from bovine dry
secretions and crystallized using the hanging-drop vapour-diffusion method. The
crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell
parameters a = 62.6, b = 67.4, c = 106.9 Angstrom. The protein was also cloned
in order to determine its complete amino-acid sequence. Its three-dimensional
structure has been determined using data to 2.1 Angstrom resolution. The
amino-acid sequence determination of SPC-40 reveals two potential
N-glycosylation sites at Asn39 and Asn345, but electron density for a glycan
chain was only present at Asn39. The protein adopts a conformation with the
classical (beta/alpha)(8)-barrel fold of triosephosphate isomerase (TIM barrel;
residues 1-237 and 310-360) with the insertion of a small alpha+beta domain
(residues 240-307) similar to that observed in chitinases. However, the
substitution of Leu for Glu in the consensus catalytic sequence in SPC-40 caused
a loss of chitinase activity. Furthermore, the chitin-binding groove in SPC-40
is considerably distorted owing to unfavourable conformations of several
residues, including Trp78, Tyr120, Asp186 and Arg242. Three surface loops,
His188-His197, Phe202-Arg212 and Tyr244-Pro260, have exceptionally high B
factors, suggesting large-scale flexibility. Fluorescence studies indicate that
various sugars bind to SPC-40 with low affinities.
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Figure 5.
Figure 5 Ribbon diagrams (DeLano, 2002[DeLano, W. L. (2002).
The PyMOL User's Manual. DeLano Scientific, San Carlos, CA,
USA.]) of SPC-40. (a) Top-view orientation showing residues
involved in carbohydrate binding (cyan) and some of those
assumed to be important in receptor recognition (gold).
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Figure 6.
Figure 6 The relative environments near the  -barrel
and Trp78 are shown for (a) SPC-40 and (b) HCgp-39. The
important interactions involving residues Asp186, Tyr120, Leu183
(Met183 in HCgp-39), Arg242, Ile272 (Thr272 in HCgp-39) as well
as solvent molecules are indicated.
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2006,
62,
953-963)
copyright 2006.
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