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PDBsum entry 1pip
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Hydrolase/hydrolase inhibitor
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PDB id
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1pip
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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 structure of papain-Succinyl-Gln-Val-Val-Ala-Ala-P-Nitroanilide complex at 1.7-A resolution: noncovalent binding mode of a common sequence of endogenous thiol protease inhibitors.
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Authors
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A.Yamamoto,
K.Tomoo,
M.Doi,
H.Ohishi,
M.Inoue,
T.Ishida,
D.Yamamoto,
S.Tsuboi,
H.Okamoto,
Y.Okada.
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Ref.
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Biochemistry, 1992,
31,
11305-11309.
[DOI no: ]
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PubMed id
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Abstract
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Succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide corresponding to a common sequence
of endogenous thiol protease inhibitors is a noncompetitive reversible inhibitor
of papain. In order to elucidate the binding mode of the inhibitor at the atomic
level, its complex with papain was crystallized at ca. pH 7.0 using the hanging
drop method, and the crystal structure was analyzed at 1.7-A resolution. The
crystal has space group P2(1)2(1)2(1), with a = 43.09, b = 102.32, c = 49.69 A,
and Z = 4. A total of 47,215 observed reflections were collected on the imaging
plates using the same single crystal, and 19,833 unique reflections with Fo >
sigma (Fo) were used for structure determination and refinement. The papain
structure was determined by use of the atomic coordinates of papain previously
reported, and then refined by the X-PLOR program. The inhibitor molecule was
located on a difference Fourier map and fitted into the electron density with
the aid of computer graphics. The complex structure was finally refined to R =
19.6% including 118 solvent molecules. The X-ray analysis of the complex crystal
shows that the inhibitor is located at the R-domain side, not in the center of
the binding site created by the R- and L-domains of papain. Such a binding mode
of the inhibitor explains well the biological behavior that the inhibitor
exhibits against papain. Comparison with the structure of papain-stefin B
complex indicates that the structure of the Gln-Val-Val-Ala-Gly sequence itself
is not necessarily the essential requisite for inhibitory activity.(ABSTRACT
TRUNCATED AT 250 WORDS)
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