PDBsum entry: 1mez

Ligase

PDB id: 1mez

Contents

Protein chain

430 a.a. *

Ligands

SO4

GDP

2SA

Metals

_MG

Waters ×121

* Residue conservation analysis

PDB id:

1mez

Name:

Ligase

Title:

Structure of the recombinant mouse-muscle adenylosuccinate s complexed with samp, gdp, so4(2-), and mg(2+)

Structure:

Adenylosuccinate synthetase. Chain: a. Synonym: adss, ampsase. 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:

2.40Å R-factor: 0.221 R-free: 0.275

Authors:

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

Key ref:

C.V.Iancu et al. (2002). Feedback inhibition and product complexes of recombinant mouse muscle adenylosuccinate synthetase. J Biol Chem, 277, 40536-40543. PubMed id: 12186864 DOI: 10.1074/jbc.M204952200

Date:

09-Aug-02 Release date: 30-Oct-02

Protein chain

P28650  (PURA1_MOUSE) -  Adenylosuccinate synthetase isozyme 1

Seq: 457 a.a.

Struc: 430 a.a.

Enzyme reactions

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

GTP + IMP + L-aspartate = GDP (Bound ligand (Het Group name = GDP) corresponds exactly) + phosphate + N(6)-(1,2-dicarboxyethyl)- AMP (Bound ligand (Het Group name = 2SA) corresponds exactly)

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

 Gene Ontology (GO) functional annotation 

• Cellular component: membrane (2 terms)
• Biological process: purine nucleotide metabolic process (2 terms)
• Biochemical function: nucleotide binding (7 terms)

reference

DOI no: 10.1074/jbc.M204952200

J Biol Chem 277:40536-40543 (2002)

PubMed id: 12186864

Feedback inhibition and product complexes of recombinant mouse muscle adenylosuccinate synthetase.

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

ABSTRACT

Adenylosuccinate synthetase governs the committed step of AMP biosynthesis, the generation of 6-phosphoryl-IMP from GTP and IMP followed by the formation of adenylosuccinate from 6-phosphoryl-IMP and l-aspartate. The enzyme is subject to feedback inhibition by AMP and adenylosuccinate, but crystallographic complexes of the mouse muscle synthetase presented here infer mechanisms of inhibition that involve potentially synergistic ligand combinations. AMP alone adopts the productive binding mode of IMP and yet stabilizes the active site in a conformation that favors the binding of Mg(2+)-IMP to the GTP pocket. On the other hand, AMP, in the presence of GDP, orthophosphate, and Mg(2+), adopts the binding mode of adenylosuccinate. Depending on circumstances then, AMP behaves as an analogue of IMP or as an analogue of adenylosuccinate. The complex of adenylosuccinate.GDP.Mg(2+).sulfate, the first structure of an adenylosuccinate-bound synthetase, reveals significant geometric distortions and tight nonbonded contacts relevant to the proposed catalytic mechanism. Adenylosuccinate forms from 6-phosphoryl-IMP and l-aspartate by the movement of the purine ring into the alpha-amino group of l-aspartate.

Selected figure(s)

Figure 2.
Fig. 2. Stereoview of AMP 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 cut-off radius of 1 Å. Dashed lines represent donor-acceptor interactions.

Figure 4.
Fig. 4. Stereoview of SAMP-product complex. Electron density covering SAMP is from an omit map (coefficients of 2 F[obs] F[calc], [calc] phases) contoured at 3 using a cut-off radius of 1 Å. Dashed lines represent donor-acceptor interactions and coordinate bonds to the Mg2+.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 40536-40543) copyright 2002.

Figures were selected by an automated process.