1MF0

Structure of the Recombinant Mouse-Muscle Adenylosuccinate Synthetase Complexed with AMP, GDP, HPO4(2-), and Mg(2+)

Summary for 1MF0

• Entry DOI: 10.2210/pdb1mf0/pdb
• Related: 1MEZ 1MF1
• Descriptor: Adenylosuccinate Synthetase, MAGNESIUM ION, PHOSPHATE ION, ... (6 entities in total)
• Functional Keywords: purine biosynthesis, gtp-binding, multigene family, ligase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm: P28650
• Total number of polymer chains: 1
• Total formula weight: 51231.00

Authors

Iancu, C.V.,Borza, T.,Fromm, H.J.,Honzatko, R.B. (deposition date: 2002-08-09, release date: 2002-10-30, Last modification date: 2024-03-13)

Primary citation

Iancu, C.V.,Borza, T.,Fromm, H.J.,Honzatko, R.B.
Feedback inhibition and product complexes of recombinant mouse muscle adenylosuccinate synthetase.
J.Biol.Chem., 277:40536-40543, 2002

PubMed 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.

PubMed: 12186864
DOI: 10.1074/jbc.M204952200

Experimental method

X-RAY DIFFRACTION (2.5 Å)