 |
PDBsum entry 1mim
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immunoglobulin
|
PDB id
|
|
|
|
1mim
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure of the FAB fragment of sdz chi621: a chimeric antibody against cd25.
|
|
|
Author
|
|
V.Mikol.
|
|
|
Ref.
|
|
Acta Crystallogr D Biol Crystallogr, 1996,
52,
534-542.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
A specific drug targeted to the IL-2 receptor on activated T lymphocytes could
limit acute immunological rejection during organ transplantation. A
high-affinity monoclonal antibody directed against the alpha-chain of the IL-2
receptor (CD25) was chimerized with the constant regions of the human IgG1 heavy
and k light chain resulting in SDZ CHII621 [Amlot, Rawlings, Fernando, Griffin,
Heinrich, Schreier, Castaigne, Moore & Sweny (1995). Transplantation, 60,
748-756]. The Fab fragment of SDZ CHI621 has been purified and crystallized
(P2(l), a = 39.58, b = 59.76, c = 102.09 A, beta = 99.98 degrees ). Its
structure has been determined by molecular replacement and refined at 2.6 A to a
crystallographic R factor of 19.7%. The protein exhibits the typical
immunoglobulin fold. The complementary determining regions (CDR's) 1 and 2 of
both heavy and light chains show similar conformations to other known reported
structures whereas the CDR3 from the light chain seems to adopt a novel type of
conformation. There is a network of interactions which maintain the CDR3 of both
chains together and limit their solvent accessibility. The interaction between
V(L) and C(L) has been strengthened by the chimerization whereas that between
V(H) and C(H)1 has been weakened.
|
|
|
|
|
|
|
|
Figure 4.
Fig. 4. Comparison of the Fab
fragment of SDZ CHI621 with
that of HyHel5. Stereoviews of
the superposition of the C '~ atoms
trace of SDZ CHI621 (plain lnes)
on that of HyHel5 (dotted lines)
(Sheriff et al., 1987). Every 40th
C '~ of SDZ CHI621 is labelld.
The pictures representig mole
cules were prepared with the
program MOLSCRIPT (Kraulis,
1991).
|
|
Figure 5.
Fig. 5. Intermolecular interactions
between the L3 and H3 loops of
SDZ CHI621. The L3 and H3
loop residues and their labels are
shown with black plain lines.
Hydrogen bonds are represented
as dashed lines and the values of
the corresponding distances are
given in Table 6.
|
|
|
|
|
|
The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(1996,
52,
534-542)
copyright 1996.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Prolonged action of a chimeric interleukin-2 receptor (cd25) monoclonal antibody used in cadaveric renal transplantation.
|
|
|
Authors
|
|
P.L.Amlot,
E.Rawlings,
O.N.Fernando,
P.J.Griffin,
G.Heinrich,
M.H.Schreier,
J.P.Castaigne,
R.Moore,
P.Sweny.
|
|
|
Ref.
|
|
Transplantation, 1995,
60,
748-756.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
