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PDBsum entry 1cib
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Effectors of the stringent response target the active site of escherichia coli adenylosuccinate synthetase.
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Authors
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Z.Hou,
M.Cashel,
H.J.Fromm,
R.B.Honzatko.
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Ref.
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J Biol Chem, 1999,
274,
17505-17510.
[DOI no: ]
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PubMed id
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Abstract
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Guanosine 5'-diphosphate 3'-diphosphate (ppGpp), a pleiotropic effector of the
stringent response, potently inhibits adenylosuccinate synthetase from
Escherichia coli as an allosteric effector and/or as a competitive inhibitor
with respect to GTP. Crystals of the synthetase grown in the presence of IMP,
hadacidin, NO3-, and Mg2+, then soaked with ppGpp, reveal electron density at
the GTP pocket which is consistent with guanosine 5'-diphosphate 2':3'-cyclic
monophosphate. Unlike ligand complexes of the synthetase involving IMP and GDP,
the coordination of Mg2+ in this complex is octahedral with the side chain of
Asp13 in the inner sphere of the cation. The cyclic phosphoryl group interacts
directly with the side chain of Lys49 and indirectly through bridging water
molecules with the side chains of Asn295 and Arg305. The synthetase either
directly facilitates the formation of the cyclic nucleotide or scavenges trace
amounts of the cyclic nucleotide from solution. Regardless of its mode of
generation, the cyclic nucleotide binds far more tightly to the active site than
does ppGpp. Conceivably, synthetase activity in vivo during the stringent
response may be sensitive to the relative concentrations of several effectors,
which together exercise precise control over the de novo synthesis of AMP.
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Figure 2.
Fig. 2. Schematic of ppG2':3'p showing atom labels.
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Figure 3.
Fig. 3. Stereoview of interactions between ppG2':3'p and
the active site. Ligands (only hadacidin (Had), nitrate,
ppG2':3'p, and Mg^2+ are shown) are drawn with bold lines.
Donor-acceptor interactions (corresponding distances listed in
Table II) are presented with dashed lines.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(1999,
274,
17505-17510)
copyright 1999.
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