PDBsum entry 1cib

Ligase

PDB id: 1cib

Contents

Protein chain

431 a.a. *

Ligands

NO3

GDP

HDA

IMP

Metals

_MG

Waters ×410

* Residue conservation analysis

PDB id:

1cib

Name:

Ligase

Title:

Structure of adenylosuccinate synthetase from e. Coli complexed with gdp, imp, hadacidin, and no3

Structure:

Adenylosuccinate synthetase. Chain: a. Synonym: ampsase. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 83333. Strain: k-12. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.30Å R-factor: 0.170 R-free: 0.240

Authors:

Z.Hou,M.Cashel,H.J.Fromm,R.B.Honzatko

Key ref:

Z.Hou et al. (1999). Effectors of the stringent response target the active site of Escherichia coli adenylosuccinate synthetase. J Biol Chem, 274, 17505-17510. PubMed id: 10364182 DOI: 10.1074/jbc.274.25.17505

Date:

31-Mar-99 Release date: 05-Apr-00

Protein chain

P0A7D4  (PURA_ECOLI) -  Adenylosuccinate synthetase from Escherichia coli (strain K12)

Seq: 432 a.a.

Struc: 431 a.a.

Enzyme reactions

• Enzyme class: E.C.6.3.4.4 - adenylosuccinate synthase.
• Pathway: AMP and GMP Biosynthesis
• Reaction: IMP + L-aspartate + GTP = N₆-(1,2-dicarboxyethyl)-AMP + GDP + phosphate + 2 H⁺

IMP + L-aspartate + GTP (Bound ligand (Het Group name = HDA) matches with 41.67% similarity) = N(6)-(1,2-dicarboxyethyl)-AMP (Bound ligand (Het Group name = GDP) corresponds exactly) + GDP + phosphate + 2 × H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.274.25.17505

J Biol Chem 274:17505-17510 (1999)

PubMed id: 10364182

Effectors of the stringent response target the active site of Escherichia coli adenylosuccinate synthetase.

Z.Hou, M.Cashel, H.J.Fromm, R.B.Honzatko.

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.

Selected figure(s)

Figure 2.
Fig. 2. Schematic of ppG2':3'p showing atom labels.

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.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1999, 274, 17505-17510) copyright 1999.

Figures were selected by an automated process.