1CH8

STRUCTURE OF ADENYLOSUCCINATE SYNTHETASE FROM E. COLI COMPLEXED WITH A STRINGENT EFFECTOR, PPG2':3'P

Summary for 1CH8

• Entry DOI: 10.2210/pdb1ch8/pdb
• Descriptor: PROTEIN (ADENYLOSUCCINATE SYNTHETASE), NITRATE ION, MAGNESIUM ION, ... (7 entities in total)
• Functional Keywords: ligase, adenylosuccinate synthetase, gtp-hydrolysing enzymes, purine 2 nucleotide biosynthesis, ppgpp, ppg2':3'p, stringent effector
• Biological source: Escherichia coli
• Cellular location: Cytoplasm: P0A7D4
• Total number of polymer chains: 1
• Total formula weight: 48328.35

Authors

Hou, Z.,Cashel, M.,Fromm, H.J.,Honzatko, R.B. (deposition date: 1999-03-31, release date: 1999-12-29, Last modification date: 2023-08-09)

Primary citation

Hou, Z.,Cashel, M.,Fromm, H.J.,Honzatko, R.B.
Effectors of the stringent response target the active site of Escherichia coli adenylosuccinate synthetase.
J.Biol.Chem., 274:17505-17510, 1999

PubMed Abstract: 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.

PubMed: 10364182
DOI: 10.1074/jbc.274.25.17505

Experimental method

X-RAY DIFFRACTION (2.5 Å)