 |
PDBsum entry 1e35
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase(serine protease)
|
PDB id
|
|
|
|
1e35
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.3.4.21.36
- pancreatic elastase.
|
|
|
|
|
|
|
Reaction:
|
|
Hydrolysis of proteins, including elastin. Preferential cleavage: Ala-|-Xaa.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
Biochem J
351:335-340
(2000)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
'pH-jump' crystallographic analyses of gamma-lactam-porcine pancreatic elastase complexes.
|
|
P.A.Wright,
R.C.Wilmouth,
I.J.Clifton,
C.J.Schofield.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
beta-Lactams inhibit a range of enzymes via acylation of nucleophilic serine
residues. Certain gamma-lactam analogues of monocyclic beta-lactams have also
been shown to be reversible inhibitors of porcine pancreatic elastase (PPE),
forming acyl-enzyme complexes that are stable with respect to hydrolysis.
Crystallographic analysis at pH 5 of an acyl-enzyme complex formed with PPE and
one of these inhibitors revealed the ester carbonyl located in the oxyanion hole
in a similar conformation to that observed in the structure of a complex formed
between a heptapeptide (beta-casomorphin-7) and PPE. Only weak electron density
was observed for the His-57 side chain in its 'native' conformation. Instead,
the His-57 side chain predominantly adopted a conformation rotated approx. 90
degrees from its normal position. PPE-gamma-lactam crystals were subjected to
'pH-jumps' by placing the crystals in a buffer of increased pH prior to freezing
for data collection. The results indicate that the conformation of the
gamma-lactam-derived acyl-enzyme species in the PPE active site is dependent on
pH, a result having implications for the analysis of other serine
protease-inhibitor structures at non-catalytic pH values. The results help to
define the stereoelectronic relationship between the ester of the acyl-enzyme
complex, the side chain of His-57 and the incoming nucleophile during the
reversible (de)acylation steps, implying it is closely analogous to the
hydrolytic deacylation step during catalytic peptide hydrolysis.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
N.Singh,
T.Jabeen,
S.Sharma,
I.Roy,
M.N.Gupta,
S.Bilgrami,
R.K.Somvanshi,
S.Dey,
M.Perbandt,
C.Betzel,
A.Srinivasan,
and
T.P.Singh
(2005).
Detection of native peptides as potent inhibitors of enzymes. Crystal structure of the complex formed between treated bovine alpha-chymotrypsin and an autocatalytically produced fragment, IIe-Val-Asn-Gly-Glu-Glu-Ala-Val-Pro-Gly-Ser-Trp-Pro-Trp, at 2.2 angstroms resolution.
|
| |
FEBS J,
272,
562-572.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
R.Villar,
M.J.Gil,
J.I.García,
and
V.Martínez-Merino
(2005).
Are AM1 ligand-protein binding enthalpies good enough for use in the rational design of new drugs?
|
| |
J Comput Chem,
26,
1347-1358.
|
|
|
|
|
|
|
M.Topf,
P.Várnai,
C.J.Schofield,
and
W.G.Richards
(2002).
Molecular dynamics simulations of the acyl-enzyme and the tetrahedral intermediate in the deacylation step of serine proteases.
|
| |
Proteins,
47,
357-369.
|
|
|
|
|
|
|
P.A.Wright,
R.C.Wilmouth,
I.J.Clifton,
and
C.J.Schofield
(2001).
Kinetic and crystallographic analysis of complexes formed between elastase and peptides from beta-casein.
|
| |
Eur J Biochem,
268,
2969-2974.
|
|
|
PDB code:
|
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
|
|
Links
