Structure of the Recombinant Mouse-Muscle Adenylosuccinate Synthetase Complexed with AMPStructure of the Recombinant Mouse-Muscle Adenylosuccinate Synthetase Complexed with AMP

Structural highlights

1mf1 is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
Gene:Adss1 (LK3 transgenic mice)
Activity:Adenylosuccinate synthase, with EC number 6.3.4.4
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PURA1_MOUSE] Component of the purine nucleotide cycle (PNC), which interconverts IMP and AMP to regulate the nucleotide levels in various tissues, and which contributes to glycolysis and ammoniagenesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.[1]

Evolutionary Conservation

 

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Feedback inhibition and product complexes of recombinant mouse muscle adenylosuccinate synthetase.,Iancu CV, Borza T, Fromm HJ, Honzatko RB J Biol Chem. 2002 Oct 25;277(43):40536-43. Epub 2002 Aug 16. PMID:12186864[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Borza T, Iancu CV, Pike E, Honzatko RB, Fromm HJ. Variations in the response of mouse isozymes of adenylosuccinate synthetase to inhibitors of physiological relevance. J Biol Chem. 2003 Feb 28;278(9):6673-9. Epub 2002 Dec 12. PMID:12482871 doi:http://dx.doi.org/10.1074/jbc.M210838200
  2. Iancu CV, Borza T, Fromm HJ, Honzatko RB. Feedback inhibition and product complexes of recombinant mouse muscle adenylosuccinate synthetase. J Biol Chem. 2002 Oct 25;277(43):40536-43. Epub 2002 Aug 16. PMID:12186864 doi:10.1074/jbc.M204952200

1mf1, resolution 2.70Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA