 |
PDBsum entry 3btf
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/hydrolase inhibitor
|
PDB id
|
|
|
|
3btf
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
The crystal structures of the complexes between bovine beta-Trypsin and ten p1 variants of bpti.
|
|
|
Authors
|
|
R.Helland,
J.Otlewski,
O.Sundheim,
M.Dadlez,
A.O.Smalås.
|
|
|
Ref.
|
|
J Mol Biol, 1999,
287,
923-942.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The high-resolution X-ray structures have been determined for ten complexes
formed between bovine beta-trypsin and P1 variants (Gly, Asp, Glu, Gln, Thr,
Met, Lys, His, Phe, Trp) of bovine pancreatic trypsin inhibitor (BPTI). All the
complexes were crystallised from the same conditions. The structures of the P1
variants Asp, Glu, Gln and Thr, are reported here for the first time in complex
with any serine proteinase. The resolution of the structures ranged from 1.75 to
2.05 A and the R-factors were about 19-20 %. The association constants of the
mutants ranged from 1.5x10(4) to 1.7x10(13) M-1. All the structures could be
fitted into well-defined electron density, and all had very similar global
conformations. All the P1 mutant side-chains could be accomodated at the primary
binding site, but relative to the P1 Lys, there were small local changes within
the P1-S1 interaction site. These comprised: (1) changes in the number and
dynamics of water molecules inside the pocket; (2) multiple conformations and
non-optimal dihedral angles for some of the P1 side-chains, Ser190 and Gln192;
and (3) changes in temperature factors of the pocket walls as well as the
introduced P1 side-chain. Binding of the cognate P1 Lys is characterised by
almost optimal dihedral angles, hydrogen bonding distances and angles, in
addition to considerably lower temperature factors. Thus, the trypsin S1 pocket
seems to be designed particularly for lysine binding.
|
|
|
|
|
|
|
|
Figure 7.
Figure 7. Superimposition of the P1-S1 binding sites of typsin-BPTI complexes of (a) P 1 Asp (red) and P1 Glu (blue)
and (b) of P1 Glu (blue) and P1 Gln (green). The P1 side-chains of Glu and Gln are both shown with two alternate
conformations. The Figure was produced using BOBSCRIPT (Kraulis 1991; Esnouf, 1997).
|
|
Figure 8.
Figure 8. Superimposition of the P1-S1 binding sites of trypsin-BPTI complexes with P 1 Trp (red), P1 Phe (green)
and P1 His (blue). The Figure was produced using BOBSCRIPT (Kraulis 1991; Esnouf, 1997).
|
|
|
|
|
|
The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1999,
287,
923-942)
copyright 1999.
|
|
|
|
|
|
|
