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PDBsum entry 1cho
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Hydrolase/hydrolase inhibitor
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PDB id
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1cho
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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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Crystal and molecular structures of the complex of alpha-Chymotrypsin with its inhibitor turkey ovomucoid third domain at 1.8 a resolution.
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Authors
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M.Fujinaga,
A.R.Sielecki,
R.J.Read,
W.Ardelt,
M.Laskowski,
M.N.James.
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Ref.
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J Mol Biol, 1987,
195,
397-418.
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PubMed id
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Abstract
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The molecular structure of the complex between bovine pancreatic
alpha-chymotrypsin (EC 3.4.4.5) and the third domain of the Kazal-type ovomucoid
from Turkey (OMTKY3) has been determined crystallographically by the molecular
replacement method. Restrained-parameter least-squares refinement of the
molecular model of the complex has led to a conventional agreement factor R of
0.168 for the 19,466 reflections in the 1.8 A (1 A = 0.1 nm) resolution shell [I
greater than or equal to sigma (I)]. The reactive site loop of OMTKY3, from
Lys13I to Arg21I (I indicates inhibitor), is highly complementary to the surface
of alpha-chymotrypsin in the complex. A total of 13 residues on the inhibitor
make 113 contacts of less than 4.0 A with 21 residues of the enzyme. A short
contact (2.95 A) from O gamma of Ser195 to the carbonyl-carbon atom of the
scissile bond between Leu18I and Glu19I is present; in spite of it, this peptide
remains planar and undistorted. Analysis of the interactions of the inhibitor
with chymotrypsin explains the enhanced specificity that chymotrypsin has for
P'3 arginine residues. There is a water-mediated ion pair between the
guanidinium group on this residue and the carboxylate of Asp64. Comparison of
the structure of the alpha-chymotrypsin portion of this complex with the several
structures of alpha and gamma-chymotrypsin in the uncomplexed form shows a high
degree of structural equivalence (root-mean-square deviation of the 234 common
alpha-carbon atoms averages 0.38 A). Significant differences occur mainly in two
regions Lys36 to Phe39 and Ser75 to Lys79. Among the 21 residues that are in
contact with the ovomucoid domain, only Phe39 and Tyr146 change their
conformations significantly as a result of forming the complex. Comparison of
the structure of the OMTKY3 domain in this complex to that of the same inhibitor
bound to a serine proteinase from Streptomyces griseus (SGPB) shows a central
core of 44 amino acids (the central alpha-helix and flanking small 3-stranded
beta-sheet) that have alpha-carbon atoms fitting to within 1.0 A
(root-mean-square deviation of 0.45 A) whereas the residues of the reactive-site
loop differ in position by up to 1.9 A (C alpha of Leu18I). The ovomucoid domain
has a built-in conformational flexibility that allows it to adapt to the active
sites of different enzymes. A comparison of the SGPB and alpha-chymotrypsin
molecules is made and the water molecules bound at the inhibitor-enzyme
interface in both complexes are analysed for similarities and differences.
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