ArticleBiochemistry2008
Structural analysis of the active site geometry of N5-carboxyaminoimidazole ribonucleotide synthetase from Escherichia coli.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- A Fragment-Based Screen for Inhibitors of Escherichia coli N5-CAIR Mutase.Research square · 2024Article
- Article
- Binding site matching in rational drug design: algorithms and applications.Briefings in bioinformatics · 2019Review
- Enzymatic strategies and biocatalysts for amide bond formation: tricks of the trade outside of the ribosome.Molecular bioSystems · 2015Review
- Intramolecular charge-assisted hydrogen bond strength in pseudochair carboxyphosphate.The journal of physical chemistry. B · 2015Article
- Site-directed mutagenesis of catalytic residues in N(5)-carboxyaminoimidazole ribonucleotide synthetase.Biochemistry · 2013Article
- Function prediction from networks of local evolutionary similarity in protein structure.BMC bioinformatics · 2013Article
- The enzymes of biotin dependent CO₂ metabolism: what structures reveal about their reaction mechanisms.Protein science : a publication of the Protein Society · 2012Review
- Purine biosynthesis in archaea: variations on a theme.Biology direct · 2011Article
- The ATP-grasp enzymes.Bioorganic chemistry · 2011Review
- Structure of N5-carboxyaminoimidazole ribonucleotide synthase (PurK) from Bacillus anthracis.Acta crystallographica. Section D, Biological crystallography · 2011Article
- Structural and biochemical characterization of N5-carboxyaminoimidazole ribonucleotide synthetase and N5-carboxyaminoimidazole ribonucleotide mutase from Staphylococcus aureus.Acta crystallographica. Section D, Biological crystallography · 2011Article
- Unlocking the sugar "steric gate" of DNA polymerases.Biochemistry · 2011Review
- Structural and functional studies of Aspergillus clavatus N(5)-carboxyaminoimidazole ribonucleotide synthetase .Biochemistry · 2010Article
- Structural and functional modularity of proteins in the de novo purine biosynthetic pathway.Protein science : a publication of the Protein Society · 2009Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
N(5)-Carboxyaminoimidazole ribonucleotide synthetase (N(5)-CAIR synthetase) converts 5-aminoimidazole ribonucleotide (AIR), MgATP, and bicarbonate into N(5)-CAIR, MgADP, and P(i). The enzyme is required for de novo purine biosynthesis in microbes yet is not found in humans suggesting that it represents an ideal and unexplored target for antimicrobial drug design. Here we report the X-ray structures of N(5)-CAIR synthetase from Escherichia coli with either MgATP or MgADP/P(i) bound in the active site cleft. These structures, determined to 1.6-A resolution, provide detailed information regarding the active site geometry before and after ATP hydrolysis. In both structures, two magnesium ions are observed. Each of these is octahedrally coordinated, and the carboxylate side chain of Glu238 bridges them. For the structure of the MgADP/P(i) complex, crystals were grown in the presence of AIR and MgATP. No electron density was observed for AIR, and the electron density corresponding to the nucleotide clearly revealed the presence of ADP and P(i) rather than ATP. The bound P(i) shifts by approximately 3 A relative to the gamma-phosphoryl group of ATP and forms electrostatic interactions with the side chains of Arg242 and His244. Since the reaction mechanism of N(5)-CAIR synthetase is believed to proceed via a carboxyphosphate intermediate, we propose that the location of the inorganic phosphate represents the binding site for stabilization of this reactive species. Using the information derived from the two structures reported here, coupled with molecular modeling, we propose a catalytic mechanism for N(5)-CAIR synthetase.
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