 |
PDBsum entry 1mtp
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Structural genomics
|
PDB id
|
|
|
|
1mtp
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
The 1.5 a crystal structure of a prokaryote serpin: controlling conformational change in a heated environment.
|
|
|
Authors
|
|
J.A.Irving,
L.D.Cabrita,
J.Rossjohn,
R.N.Pike,
S.P.Bottomley,
J.C.Whisstock.
|
|
|
Ref.
|
|
Structure, 2003,
11,
387-397.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Serpins utilize conformational change to inhibit target proteinases; the price
paid for this conformational flexibility is that many undergo
temperature-induced polymerization. Despite this thermolability, serpins are
present in the genomes of thermophilic prokaryotes, and here we characterize the
first such serpin, thermopin. Thermopin is a proteinase inhibitor and, in
comparison with human alpha(1)-antitrypsin, possesses enhanced stability at 60
degrees C. The 1.5 A crystal structure reveals novel structural features in
regions implicated in serpin folding and stability. Thermopin possesses a
C-terminal "tail" that interacts with the top of the A beta sheet and
plays an important role in the folding/unfolding of the molecule. These data
provide evidence as to how this unusual serpin has adapted to fold and function
in a heated environment.
|
|
|
|
|
|
Figure 1.
Figure 1. A Schematic Summarizing the Inhibitory Mechanism
of SerpinsThe RCL is the region responsible for interacting with
target proteinases and is at the top of the molecule. Residues
within the RCL are numbered according to Schecter and Berger
[78], in which the residues of a peptide substrate are
designated P[n]...P[2], P[1], and P[1]'...P[n]', and interact
with corresponding subsites in the proteinase, designated
S[n]...S[2], S[1], and S[1]'...S[n]'; cleavage occurs by
definition between the P[1] and P[1]' positions. The proteinase
(denoted by "P") recognizes the RCL sequence and cleaves the
serpin between P[1] and P[1]'; after this, prior to hydrolysis
of the acyl bond that links enzyme to inhibitor, the RCL inserts
into the central "A" b sheet. The proteinase is thereby
translocated to the distal end of the molecule, where it is
compressed against the base of the serpin and its active site is
distorted.
|
|
|
|
|
|
The above figure is
reprinted
by permission from Cell Press:
Structure
(2003,
11,
387-397)
copyright 2003.
|
|
|
|
|
|
|
