1cib
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STRUCTURE OF ADENYLOSUCCINATE SYNTHETASE FROM E. COLI COMPLEXED WITH GDP, IMP, HADACIDIN, AND NO3
OverviewOverview
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.
About this StructureAbout this Structure
1CIB is a Single protein structure of sequence from Escherichia coli with NO3, MG, GDP, HDA and IMP as ligands. Active as Adenylosuccinate synthase, with EC number 6.3.4.4 Full crystallographic information is available from OCA.
ReferenceReference
Effectors of the stringent response target the active site of Escherichia coli adenylosuccinate synthetase., Hou Z, Cashel M, Fromm HJ, Honzatko RB, J Biol Chem. 1999 Jun 18;274(25):17505-10. PMID:10364182
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