PDBsum entry 1loo

Ligase

PDB id: 1loo

Contents

Protein chain

431 a.a. *

Ligands

GTP

Waters ×100

* Residue conservation analysis

PDB id:

1loo

Name:

Ligase

Title:

Crystal structure of the mouse-muscle adenylosuccinate synthetase ligated with gtp

Structure:

Adenylosuccinate synthetase. Chain: a. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: adss1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.20Å R-factor: 0.244 R-free: 0.276

Authors:

C.V.Iancu,T.Borza,H.J.Fromm,R.B.Honzatko

Key ref:

C.V.Iancu et al. (2002). IMP, GTP, and 6-phosphoryl-IMP complexes of recombinant mouse muscle adenylosuccinate synthetase. J Biol Chem, 277, 26779-26787. PubMed id: 12004071 DOI: 10.1074/jbc.M203730200

Date:

06-May-02 Release date: 28-Aug-02

Protein chain

P28650  (PURA1_MOUSE) -  Adenylosuccinate synthetase isozyme 1 from Mus musculus

Seq: 457 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 (Bound ligand (Het Group name = GTP) corresponds exactly) + L-aspartate + GTP = N(6)-(1,2-dicarboxyethyl)-AMP + GDP + phosphate + 2 × H(+)

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

reference

DOI no: 10.1074/jbc.M203730200

J Biol Chem 277:26779-26787 (2002)

PubMed id: 12004071

IMP, GTP, and 6-phosphoryl-IMP complexes of recombinant mouse muscle adenylosuccinate synthetase.

C.V.Iancu, T.Borza, H.J.Fromm, R.B.Honzatko.

ABSTRACT

Prokaryotes have a single form of adenylosuccinate synthetase that controls the committed step of AMP biosynthesis, but vertebrates have two isozymes of the synthetase. The basic isozyme, which predominates in muscle, participates in the purine nucleotide cycle, has an active site conformation different from that of the Escherichia coli enzyme, and exhibits significant differences in ligand recognition. Crystalline complexes presented here of the recombinant basic isozyme from mouse show the following. GTP alone binds to the active site without inducing a conformational change. IMP in combination with an acetate anion induces major conformational changes and organizes the active site for catalysis. IMP, in the absence of GTP, binds to the GTP pocket of the synthetase. The combination of GTP and IMP results in the formation of a stable complex of 6-phosphoryl-IMP and GDP in the presence or absence of hadacidin. The response of the basic isozyme to GTP alone differs from that of synthetases from plants, and yet the conformation of the mouse basic and E. coli synthetases in their complexes with GDP, 6-phosphoryl-IMP, and hadacidin are nearly identical. Hence, reported differences in ligand recognition among synthetases probably arise from conformational variations observed in partially ligated enzymes.

Selected figure(s)

Figure 2.
Fig. 2. Stereoview of GTP bound to the active site. Electron density is from an omit map (coefficients of 2F[obs] F[calc], [calc] phases) contoured at 3 using a cutoff radius of 1 Å. Dashed lines represent donor-acceptor interactions.

Figure 6.
Fig. 6. Stereoview of the 6PIMP·GDP·hadacidin complex. One molecule of 6PIMP, GDP, and hadacidin bind to the single, symmetry-unique subunit in this crystal form ( top). Electron density is from an omit map (coefficients of 2F[obs] F[calc], [calc] phases) contoured at 3 using a cutoff radius of 1 Å. Dashed lines represent donor-acceptor interactions. Only the new interactions, relative to GDP·6PIMP complex, are shown. Additional details are in "Results."

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 26779-26787) copyright 2002.

Figures were selected by an automated process.