 |
PDBsum entry 1ppp
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase(sulfhydryl proteinase)
|
PDB id
|
|
|
|
1ppp
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure of papain-E64-C complex. Binding diversity of e64-C to papain s2 and s3 subsites.
|
|
|
Authors
|
|
M.J.Kim,
D.Yamamoto,
K.Matsumoto,
M.Inoue,
T.Ishida,
H.Mizuno,
S.Sumiya,
K.Kitamura.
|
|
|
Ref.
|
|
Biochem J, 1992,
287,
797-803.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
In order to investigate the binding mode of E64-c (a synthetic cysteine
proteinase inhibitor) to papain at the atomic level, the crystal structure of
the complex was analysed by X-ray diffraction at 1.9 A (1 A is expressed in SI
units as 0.1 nm) resolution. The crystal has a space group P2(1)2(1)2(1) with a
= 43.37, b = 102.34 and c = 49.95 A. A total of 21,135 observed reflections were
collected from the same crystal, and 14811 unique reflections of up to 1.9 A
resolution [Fo > 3 sigma(Fo)] were used for the structure solution and
refinement. The papain structure was determined by means of the molecular
replacement method, and then the inhibitor was observed on a (2 magnitude of
Fo-magnitude of Fc) difference Fourier map. The complex structure was finally
refined to R = 19.4% including 207 solvent molecules. Although this complex
crystal (Form II) was polymorphous as compared with the previously analysed one
(Form I), the binding modes of leucine and isoamylamide moieties of E64-c were
significantly different from each other. By the calculation of accessible
surface area for each complex atom, these two different binding modes were both
shown to be tight enough to prevent the access of solvent molecules to the
papain active site. With respect to the E64-c-papain binding mode,
molecular-dynamics simulations proposed two kinds of stationary states which
were derived from the crystal structures of Forms I and II. One of these, which
corresponds to the binding mode simulated from Form I, was essentially the same
as that observed in the crystal structure, and the other was somewhat different
from the crystal structure of Form II, especially with respect to the binding of
the isoamylamide moiety with the papain S subsites. The substrate specificity
for the papain active site is discussed on the basis of the present results.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Refined X-Ray structure of papain.E-64-C complex at 2.1-A resolution.
|
|
|
Authors
|
|
D.Yamamoto,
K.Matsumoto,
H.Ohishi,
T.Ishida,
M.Inoue,
K.Kitamura,
H.Mizuno.
|
|
|
Ref.
|
|
J Biol Chem, 1991,
266,
14771-14777.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #2
|
|
|
Title
|
|
Mode of binding of e-64-C, A potent thiol protease inhibitor, To papain as determined by X-Ray crystal analysis of the complex.
|
|
|
Authors
|
|
K.Matsumoto,
D.Yamamoto,
H.Ohishi,
K.Tomoo,
T.Ishida,
M.Inoue,
T.Sadatome,
K.Kitamura,
H.Mizuno.
|
|
|
Ref.
|
|
FEBS Lett, 1989,
245,
177-180.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #3
|
|
|
Title
|
|
The importance of val-157 hydrophobic interaction for papain inhibitory activity of an epoxysuccinyl amino acid derivative. A structure-Activity relationship based on the crystal structure of the papain-E-64-C complex.
|
|
|
Authors
|
|
D.Yamamoto,
K.Matsumoto,
H.Ohishi,
T.Ishida,
M.Inoue,
K.Kitamura,
K.Hanada.
|
|
|
Ref.
|
|
FEBS Lett, 1990,
263,
134-136.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
