1a48

File:1a48.gif

spinqualitylabelsall models 1a48, resolution 1.9Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

SAICAR SYNTHASE

OverviewOverview

BACKGROUND: The biosynthesis of key metabolic components is of major, interest to biologists. Studies of de novo purine synthesis are aimed at, obtaining a deeper understanding of this central pathway and the, development of effective chemotherapeutic agents., Phosphoribosylaminoimidazolesuccinocarboxamide (SAICAR) synthase catalyses, the seventh step out of ten in the biosynthesis of purine nucleotides. To, date, only one structure of an enzyme involved in purine biosynthesis has, been reported: adenylosuccinate synthetase, which catalyses the first, committed step in the synthesis of AMP from IMP. RESULTS: We report the, first three-dimensional structure of a SAICAR synthase, from Saccharomyces, cerevisiae. It is a monomer with three domains. The first two domains, consist of antiparallel beta sheets and the third is composed of two alpha, helices. There is a long deep cleft made up of residues from all three, domains. Comparison of SAICAR synthases by alignment of their sequences, reveals a number of conserved residues, mostly located in the cleft. The, presence of two sulphate ions bound in the cleft, the structure of SAICAR, synthase in complex with ATP and a comparison of this structure with that, of other ATP-dependent proteins point to the interdomain cleft as the, location of the active site. CONCLUSIONS: The topology of the first domain, of SAICAR synthase resembles that of the N-terminal domain of proteins, belonging to the cyclic AMP-dependent protein kinase family. The fold of, the second domain is similar to that of members of the D-alanine:D-alanine, ligase family. Together these enzymes form a new superfamily of, mononucleotide-binding domains. There appears to be no other enzyme, however, which is composed of the same combination of three domains, with, the individual topologies found in SAICAR synthase.

About this StructureAbout this Structure

1A48 is a Single protein structure of sequence from Saccharomyces cerevisiae with SO4 and ACE as ligands. Active as Phosphoribosylaminoimidazolesuccinocarboxamide synthase, with EC number 6.3.2.6 Full crystallographic information is available from OCA.

ReferenceReference

The structure of SAICAR synthase: an enzyme in the de novo pathway of purine nucleotide biosynthesis., Levdikov VM, Barynin VV, Grebenko AI, Melik-Adamyan WR, Lamzin VS, Wilson KS, Structure. 1998 Mar 15;6(3):363-76. PMID:9551557

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