1mf0
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Structure of the Recombinant Mouse-Muscle Adenylosuccinate Synthetase Complexed with AMP, GDP, HPO4(2-), and Mg(2+)
OverviewOverview
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.
About this StructureAbout this Structure
1MF0 is a Single protein structure of sequence from Mus musculus with MG, PO4, AMP and GDP as ligands. Active as Adenylosuccinate synthase, with EC number 6.3.4.4 Full crystallographic information is available from OCA.
ReferenceReference
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
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