 |
PDBsum entry 1bll
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/hydrolase inhibitor
|
PDB id
|
|
|
|
1bll
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
X-Ray crystallographic determination of the structure of bovine lens leucine aminopeptidase complexed with amastatin: formulation of a catalytic mechanism featuring a gem-Diolate transition state.
|
|
|
Authors
|
|
H.Kim,
W.N.Lipscomb.
|
|
|
Ref.
|
|
Biochemistry, 1993,
32,
8465-8478.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The structure of the complex of bovine lens leucine aminopeptidase (blLAP) with
the slow-, tight-binding inhibitor amastatin has been determined by X-ray
crystallography. X-ray diffraction data were collected at -150 degrees C from a
single blLAP-amastatin crystal which under the data collection conditions was of
the space group P6(3)22 with unit cell parameters a = 130.3 A and c = 121.9 A.
The structure of the blLAP-amastatin complex was determined by molecular
replacement, using the structure of native blLAP as the starting model.
Refinement of the blLAP-amastatin model plus 132 water molecules against data
from 10.0- to 2.4-A resolution resulted in a final structure with a
crystallographic residual of 0.198. The binding mode of amastatin is similar to
that of bestatin, the structure of whose complex with blLAP has previously been
determined. Of particular note, the N-terminus-to-C-terminus orientation of the
two bound inhibitors is the same. The two N-terminal residues of amastatin and
bestatin occupy the same binding sites, which are most likely S1 and S'1. The
slow binding of amastatin and bestatin may be partially attributable to a
binding mechanism in which the two active site metals are sequentially
coordinated by the P1 amino and hydroxyl groups of these inhibitors. A catalytic
mechanism for blLAP is proposed based on the binding modes of amastatin and
bestatin and plausible binding modes of a dipeptide substrate and its putative
gem-diolate transition state which were modeled into the active site of blLAP
after the binding mode of amastatin. The proposed catalytic mechanism invokes
roles for the catalytic metals in binding and activating the substrate and in
stabilizing the transition state. The mechanism also includes roles for Asp-255
as a general base, Arg-336 as an additional electrophilic substrate activator
and transition state stabilizer, and Lys-262 as a proton shuttle.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Structure determination and refinement of bovine lens leucine aminopeptidase and its complex with bestatin.
|
|
|
Authors
|
|
S.K.Burley,
P.R.David,
R.M.Sweet,
A.Taylor,
W.N.Lipscomb.
|
|
|
Ref.
|
|
J Mol Biol, 1992,
224,
113-140.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #2
|
|
|
Title
|
|
Leucine aminopeptidase: bestatin inhibition and a model for enzyme-Catalyzed peptide hydrolysis.
|
|
|
Authors
|
|
S.K.Burley,
P.R.David,
W.N.Lipscomb.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 1991,
88,
6916-6920.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #3
|
|
|
Title
|
|
Molecular structure of leucine aminopeptidase at 2.7-A resolution.
|
|
|
Authors
|
|
S.K.Burley,
P.R.David,
A.Taylor,
W.N.Lipscomb.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 1990,
87,
6878-6882.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
