 |
PDBsum entry 5e8d
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
5e8d
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
43 a.a.
|
|
|
|
|
|
|
|
|
|
|
216 a.a.
|
|
|
|
|
|
|
|
|
|
|
210 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Immune system
|
|
|
Title:
|
|
Crystal structure of human epiregulin in complex with the fab fragment of murine monoclonal antibody 9e5
|
|
Structure:
|
|
Proepiregulin. Chain: a. Engineered: yes. Anti-human epiregulin antibody 9e5 fab heavy chain. Chain: h. Anti-human epiregulin antibody 9e5 fab light chain. Chain: l
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: ereg. Expressed in: escherichia coli. Expression_system_taxid: 562. Mus musculus. Organism_taxid: 10090. Organism_taxid: 10090
|
|
Resolution:
|
|
|
2.50Å
|
R-factor:
|
0.193
|
R-free:
|
0.263
|
|
|
Authors:
|
|
Y.Kado,E.Mizohata,S.Nagatoishi,M.Iijima,K.Shinoda,T.Miyafusa, T.Nakayama,T.Yoshizumi,A.Sugiyama,T.Kawamura,Y.H.Lee,H.Matsumura, H.Doi,H.Fujitani,T.Kodama,Y.Shibasaki,K.Tsumoto,T.Inoue
|
|
Key ref:
|
|
Y.Kado
et al.
(2016).
Epiregulin Recognition Mechanisms by Anti-epiregulin Antibody 9E5: STRUCTURAL, FUNCTIONAL, AND MOLECULAR DYNAMICS SIMULATION ANALYSES.
J Biol Chem,
291,
2319-2330.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
14-Oct-15
|
Release date:
|
09-Dec-15
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
O14944
(EREG_HUMAN) -
Proepiregulin from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
169 a.a.
43 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
J Biol Chem
291:2319-2330
(2016)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Epiregulin Recognition Mechanisms by Anti-epiregulin Antibody 9E5: STRUCTURAL, FUNCTIONAL, AND MOLECULAR DYNAMICS SIMULATION ANALYSES.
|
|
Y.Kado,
E.Mizohata,
S.Nagatoishi,
M.Iijima,
K.Shinoda,
T.Miyafusa,
T.Nakayama,
T.Yoshizumi,
A.Sugiyama,
T.Kawamura,
Y.H.Lee,
H.Matsumura,
H.Doi,
H.Fujitani,
T.Kodama,
Y.Shibasaki,
K.Tsumoto,
T.Inoue.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Epiregulin (EPR) is a ligand of the epidermal growth factor (EGF) family that
upon binding to its epidermal growth factor receptor (EGFR) stimulates
proliferative signaling, especially in colon cancer cells. Here, we describe the
three-dimensional structure of the EPR antibody (the 9E5(Fab) fragment) in the
presence and absence of EPR. Among the six complementarity-determining regions
(CDRs), CDR1-3 in the light chain and CDR2 in the heavy chain predominantly
recognize EPR. In particular, CDR3 in the heavy chain dramatically moves with
cis-trans isomerization of Pro(103). A molecular dynamics simulation and
mutational analyses revealed that Arg(40) in EPR is a key residue for the
specific binding of 9E5 IgG. From isothermal titration calorimetry analysis, the
dissociation constant was determined to be 6.5 nm. Surface plasmon resonance
analysis revealed that the dissociation rate of 9E5 IgG is extremely slow. The
superimposed structure of 9E5(Fab)·EPR on the known complex structure of
EGF·EGFR showed that the 9E5(Fab) paratope overlaps with Domains I and III on
the EGFR, which reveals that the 9E5(Fab)·EPR complex could not bind to the
EGFR. The 9E5 antibody will also be useful in medicine as a neutralizing
antibody specific for colon cancer.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
| |
Links
