 |
PDBsum entry 1fpc
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/hydrolase inhibitor
|
PDB id
|
|
|
|
1fpc
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Active-Site mimetic inhibition of thrombin.
|
|
|
Authors
|
|
I.I.Mathews,
A.Tulinsky.
|
|
|
Ref.
|
|
Acta Crystallogr D Biol Crystallogr, 1995,
51,
550-559.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
78%.
|
|
|
|
Abstract
|
|
|
The structures of two mimetic inhibitor complexes of human alpha-thrombin have
been determined by X-ray crystallography. One mimics a beta-turn with a bicyclic
ring system; the other mimics two different active-site binding modes. The
beta-turn mimetic is used to approximate a turn found in the conformation of
fibrinopeptide A, which is catalytically released by thrombin in the activation
of fibrinogen to fibrin. The binding of the second mimetic is a hybrid between
normal substrate and the abnormal binding of the potent natural leech inhibitor
hirudin. The binding of the beta-turn mimetic is tenuous, because it is like a
substrate, while that of the substrate-hirudin hybrid is that of a tenacious
inhibitor (which it is). Structurally retrospect modifications for rational
design and improvement of both mimetic inhibitors are proposed.
|
|
|
|
|
|
|
|
Figure 1.
Fig. 1. Thrombin peptide substrate-
inhibitor complexes. The asterisk
indicates sulfated tyrosine.
|
|
Figure 2.
Fig. 2. Mimetic inhibitors of thrombin. (a) FPAM, (b) DAPA, (c)
FPAM 1. Special restraints applied to non-amino-acid groups during
refinement to maintain geometry: arrow, bond distance; dotted, angle
distance, double arrow, planar 1,4 distance and NB--B 1 --B3--B4,
B2--B3--B5--NB in DAPA.
|
|
|
|
|
|
The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(1995,
51,
550-559)
copyright 1995.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
The structure of a designed peptidomimetic inhibitor complex of alpha-Thrombin.
|
|
|
Authors
|
|
T.P.Wu,
V.Yee,
A.Tulinsky,
R.A.Chrusciel,
H.Nakanishi,
R.Shen,
C.Priebe,
M.Kahn.
|
|
|
Ref.
|
|
Protein Eng, 1993,
6,
471-478.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #2
|
|
|
Title
|
|
Active site and exosite binding of alpha-Thrombin.
|
|
|
Authors
|
|
A.Tulinsky,
X.Qiu.
|
|
|
Ref.
|
|
Blood Coagul Fibrinolysis, 1993,
4,
305-312.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #3
|
|
|
Title
|
|
Interactions of a fluorescent active-Site-Directed inhibitor of thrombin: dansylarginine n-(3-Ethyl-1,5-Pentanediyl)amide.
|
|
|
Authors
|
|
M.E.Nesheim,
F.G.Prendergast,
K.G.Mann.
|
|
|
Ref.
|
|
Biochemistry, 1979,
18,
996.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
