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PDBsum entry 1cew
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Proteinase inhibitor(cysteine)
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PDB id
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1cew
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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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The 2.0 a X-Ray crystal structure of chicken egg white cystatin and its possible mode of interaction with cysteine proteinases.
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Authors
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W.Bode,
R.Engh,
D.Musil,
U.Thiele,
R.Huber,
A.Karshikov,
J.Brzin,
J.Kos,
V.Turk.
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Ref.
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Embo J, 1988,
7,
2593-2599.
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PubMed id
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Abstract
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The crystal structure of chicken egg white cystatin has been solved by X-ray
diffraction methods using the multiple isomorphous replacement technique. Its
structure has been refined to a crystallographic R value of 0.19 using X-ray
data between 6 and 2.0A. The molecule consists mainly of a straight five-turn
alpha-helix, a five-stranded antiparallel beta-pleated sheet which is twisted
and wrapped around the alpha-helix and an appending segment of partially
alpha-helical geometry. The 'highly conserved' region from Gln53I to Gly57I
implicated with binding to cysteine proteinases folds into a tight beta-hairpin
loop which on opposite sides is flanked by the amino-terminal segment and by a
second hairpin loop made up of the similarly conserved segment Pro103I -
Trp104I. These loops and the amino-terminal Gly9I - Ala10I form a wedge-shaped
'edge' which is quite complementary to the 'active site cleft' of papain.
Docking experiments suggest a unique model for the interaction of cystatin and
papain: according to it both hairpin loops of cystatin make major binding
interactions with the highly conserved residues Gly23, Gln19, Trp177 and Ala136
of papain in the neighbourhood of the reactive site Cys25; the amino-terminal
segment Gly9I - Ala10I of bound cystatin is directed towards the substrate
subsite S2, but in an inappropriate conformation and too far away to be attacked
by the reactive site Cys25. As a consequence, the mechanism of the interaction
between cysteine proteinases and their cystatin-like inhibitors seems to be
fundamentally different from the 'standard mechanism' defined for serine
proteinases and most of their protein inhibitors.
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Secondary reference #1
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Title
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Conformational variability of chicken cystatin. Comparison of structures determined by X-Ray diffraction and nmr spectroscopy.
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Authors
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R.A.Engh,
T.Dieckmann,
W.Bode,
E.A.Auerswald,
V.Turk,
R.Huber,
H.Oschkinat.
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Ref.
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J Mol Biol, 1993,
234,
1060-1069.
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PubMed id
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Secondary reference #2
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Title
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The structures of native phosphorylated chicken cystatin and of a recombinant unphosphorylated variant in solution.
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Authors
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T.Dieckmann,
L.Mitschang,
M.Hofmann,
J.Kos,
V.Turk,
E.A.Auerswald,
R.Jaenicke,
H.Oschkinat.
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Ref.
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J Mol Biol, 1993,
234,
1048-1059.
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PubMed id
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Secondary reference #3
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Title
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The cystatins: protein inhibitors of cysteine proteinases.
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Authors
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V.Turk,
W.Bode.
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Ref.
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FEBS Lett, 1991,
285,
213-219.
[DOI no: ]
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PubMed id
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Secondary reference #4
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Title
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Mechanism of interaction of cysteine proteinases and their protein inhibitors as compared to the serine proteinase-Inhibitor interaction.
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Authors
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W.Bode,
R.Engh,
D.Musil,
B.Laber,
M.Stubbs,
R.Huber,
V.Turk.
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Ref.
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Biol Chem Hoppe Seyler, 1990,
371,
111-118.
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PubMed id
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Secondary reference #5
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Title
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Mechanism of inhibition of papain by chicken egg white cystatin. Inhibition constants of n-Terminally truncated forms and cyanogen bromide fragments of the inhibitor.
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Authors
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W.Machleidt,
U.Thiele,
B.Laber,
I.Assfalg-Machleidt,
A.Esterl,
G.Wiegand,
J.Kos,
V.Turk,
W.Bode.
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Ref.
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Febs Lett, 1989,
243,
234-238.
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PubMed id
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Secondary reference #6
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Title
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The cysteine proteinase inhibitor chicken cystatin is a phosphoprotein.
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Authors
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B.Laber,
K.Krieglstein,
A.Henschen,
J.Kos,
V.Turk,
R.Huber,
W.Bode.
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Ref.
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Febs Lett, 1989,
248,
162-168.
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PubMed id
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