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PDBsum entry 1a48
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Atp binding protein
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PDB id
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1a48
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References listed in PDB file
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Key reference
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Title
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The structure of saicar synthase: an enzyme in the de novo pathway of purine nucleotide biosynthesis.
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Authors
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V.M.Levdikov,
V.V.Barynin,
A.I.Grebenko,
W.R.Melik-Adamyan,
V.S.Lamzin,
K.S.Wilson.
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Ref.
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Structure, 1998,
6,
363-376.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
Figure 1. Schematic representation of the biosynthesis of
purine nucleotides in S. cerevisiae. For each step, the name of
the enzyme and the structural gene (in parentheses) are given.
The reaction catalysed by SAICAR synthase is shown in red.
Abbreviations: AICAR, phosphoribosylaminoimidazolecarboxamide;
AIR, phosphoribosylaminoimidazole; CAIR,
phosphoribosylcarboxyaminoimidazole; FAICAR,
phosphoribosylformylaminoimidazolecarboxamide; FGAM,
phosphoribosylformylglycinamidine; FGAR,
phosphoribosylformylglycinamide; GAR, phosphoribosylglycinamide;
PR, 5-phosphoribosyl; PRA, phosphoribosylamine; PRPP,
5-phosphoribosyl 1-pyrophosphate.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1998,
6,
363-376)
copyright 1998.
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Secondary reference #1
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Title
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[Substrate specificity of phosphoribosyl-Aminoimidazole-Succinocarboxamide synthetase (saicar-Synthetase) from saccharomyces cerevisiae yeast].
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Authors
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V.V.Alenin,
K.V.Ostanin,
T.R.Kostikova,
V.D.Domkin,
V.A.Zubova,
M.N.Smirnov.
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Ref.
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Biokhimiia, 1992,
57,
845-855.
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PubMed id
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Secondary reference #2
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Title
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Crystallization and preliminary X-Ray investigation of phosphoribosylaminoimidazolesuccinocarboxamide synthase from the yeast saccharomyces cerevisiae.
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Authors
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A.I.Grebenko,
V.M.Levdikov,
V.V.Barynin,
W.R.Melik-Adamyan,
A.N.Myasnikov.
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Ref.
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J Mol Biol, 1992,
228,
298-299.
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PubMed id
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Secondary reference #3
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Title
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De novo purine nucleotide biosynthesis.
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Authors
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H.Zalkin,
J.E.Dixon.
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Ref.
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Prog Nucleic Acid Res Mol Biol, 1992,
42,
259-287.
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PubMed id
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Secondary reference #4
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Title
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The saccharomyces cerevisiae ade1 gene: structure, Overexpression and possible regulation by general amino acid control.
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Authors
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A.N.Myasnikov,
K.V.Sasnauskas,
A.A.Janulaitis,
M.N.Smirnov.
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Ref.
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Gene, 1991,
109,
143-147.
[DOI no: ]
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PubMed id
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Secondary reference #5
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Title
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[Isolation and properties of phosphoribosyl-Aminoimidazole-Succinocarboxyamide-Synthestase from saccharomyces cerevisiae yeasts].
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Authors
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K.V.Ostanin,
V.V.Alenin,
V.D.Domkin,
M.N.Smirnov.
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Ref.
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Biokhimiia, 1989,
54,
1265-1273.
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PubMed id
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Secondary reference #6
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Title
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[Nucleotide sequence of the ade 1 gene of the yeast saccharomyces cerevisiae].
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Authors
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A.N.Miasnikov,
I.U.A.Plavnik,
K.V.Sasnauskas,
G.K.Gedminene,
A.A.Ianulaĭtis.
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Ref.
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Bioorg Khim, 1986,
12,
555-558.
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PubMed id
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