 |
PDBsum entry 1trn
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase (serine proteinase)
|
PDB id
|
|
|
|
1trn
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure of human trypsin 1: unexpected phosphorylation of tyr151.
|
|
|
Authors
|
|
C.Gaboriaud,
L.Serre,
O.Guy-Crotte,
E.Forest,
J.C.Fontecilla-Camps.
|
|
|
Ref.
|
|
J Mol Biol, 1996,
259,
995.
[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
88%.
|
|
|
|
Abstract
|
|
|
The X-ray structure of human trypsin 1 has been determined in the presence of
diisopropyl-phosphofluoridate by the molecular replacement method and refined at
a resolution of 2.2 A to an R-factor of 18%. Crystals belong to the space group
P4, with two independent molecules in the asymmetric unit packing as
crystallographic tetramers. This study was performed in order to seek possible
structural peculiarities of human trypsin 1, suggested by some striking
differences in its biochemical behavior as compared to other trypsins of
mammalian species. Its fold is, in fact, very similar to those of the bovine,
rat and porcine trypsins, with root-mean-square differences in the 0.4 to 0.6 A
range for all 223 C alpha positions. The most unexpected feature of the human
trypsin 1 structure is in the phosphorylated state of tyrosine residue 151 in
the present X-ray study. This feature was confirmed by mass spectrometry on the
same inhibited sample and also on the native enzyme. This phosphorylation
strengthens the outstanding clustering of highly negative or highly positive
electrostatic surface potentials. The peculiar inhibitory behaviour of
pancreatic secretory trypsin inhibitors of the Kazal type on this enzyme is
discussed as a possible consequence of these properties. A charged surface loop
has also been interpreted as an epitope site recognised by a monoclonal antibody
specific to human trypsin 1.
|
|
|
|
|
|
|
|
Figure 6.
Figure 6. Stereo view of the (2Fo - Fc) electron density map around the active site superposed on the refined model
containing the serine-bound diisopropyl phosphate. The electron density map was contoured at the 1s level. Hydrogen
bonds are drawn with broken lines.
|
|
Figure 7.
Figure 7. Stereo view of the (2Fo - Fc) electron density map around the phosphotyrosine residue 151, superposed
on the refined model. The electron density map was contoured at the 1s level. All residues within 5 Å of the Tyr151
hydroxyl group are displayed.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1996,
259,
995-0)
copyright 1996.
|
|
|
|
|
|
|
