 |
PDBsum entry 2fpp
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Interactions of gtp with the ATP-Grasp domain of gtp-Specific succinyl-Coa synthetase.
|
|
|
Authors
|
|
M.E.Fraser,
K.Hayakawa,
M.S.Hume,
D.G.Ryan,
E.R.Brownie.
|
|
|
Ref.
|
|
J Biol Chem, 2006,
281,
11058-11065.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
Two isoforms of succinyl-CoA synthetase exist in mammals, one specific for ATP
and the other for GTP. The GTP-specific form of pig succinyl-CoA synthetase has
been crystallized in the presence of GTP and the structure determined to 2.1 A
resolution. GTP is bound in the ATP-grasp domain, where interactions of the
guanine base with a glutamine residue (Gln-20beta) and with backbone atoms
provide the specificity. The gamma-phosphate interacts with the side chain of an
arginine residue (Arg-54beta) and with backbone amide nitrogen atoms, leading to
tight interactions between the gamma-phosphate and the protein. This contrasts
with the structures of ATP bound to other members of the family of ATP-grasp
proteins where the gamma-phosphate is exposed, free to react with the other
substrate. To test if GDP would interact with GTP-specific succinyl-CoA
synthetase in the same way that ADP interacts with other members of the family
of ATP-grasp proteins, the structure of GDP bound to GTP-specific succinyl-CoA
synthetase was also determined. A comparison of the conformations of GTP and GDP
shows that the bases adopt the same position but that changes in conformation of
the ribose moieties and the alpha- and beta-phosphates allow the gamma-phosphate
to interact with the arginine residue and amide nitrogen atoms in GTP, while the
beta-phosphate interacts with these residues in GDP. The complex of GTP with
succinyl-CoA synthetase shows that the enzyme is able to protect GTP from
hydrolysis when the active-site histidine residue is not in position to be
phosphorylated.
|
|
|
|
|
|
|
|
Figure 1.
FIGURE 1. A, ribbon diagram of pig GTP-specific SCS showing
the location of the GTP-binding site. The  -subunit is green, the
 -subunit is yellow,
except for the T-loop, which is highlighted in magenta. GTP, the
potassium ion, and the side chain of the phosphorylated
histidine residue, His-259 , are drawn as stick
models and colored according to atom type: red for oxygen,
yellow for carbon, blue for nitrogen, green for phosphorus, and
turquoise for potassium. B, stereo view of the electron density
for GTP and the potassium ion, including nearby residues of the
ATP-grasp domain of pig GTP-specific SCS. The F[o] - F[c], [c]
electron density map calculated without GTP and the potassium
ion is contoured at 3  . C, stereo view of the
electron density for GDP and the potassium ion, including nearby
residues of the ATP-grasp domain of pig GTP-specific SCS. The
F[o] - F[c], [c] electron density
map calculated without GDP and the potassium ion is contoured at
3 .
The same atom colors were used in B and C as described for A.
All parts of the figure were drawn using the program RASTER3D
(58), and B and C also used the program XFIT (47).
|
|
Figure 3.
FIGURE 3. Stereo views of the superpositions of GTP bound
to pig GTP-specific SCS (black) with ADP bound to E. coli SCS
(gray) (Protein Data Bank (43) identifier 1cqi (7)) (A), GDP
bound to pig GTP-specific SCS (gray) (B), and ATP bound to
glycinamide ribonucleotide transformylase (gray) (PDB identifier
1kj8) (54) (C). The superpositions were based on structurally
similar residues and performed using the program O (51) with a
cutoff of 3.8 Å. Possible hydrogen-bonding interactions
and ionic interactions between GTP and the pig GTP-specific SCS
are represented by black dashed lines.
|
|
|
|
|
|
The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
11058-11065)
copyright 2006.
|
|
|
|
|
|
|
