Year: 2019
Type: article
Abstract: BACKGROUND: Ribose-phosphate pyrophosphokinase (EC 2.7.6.1) is an enzyme that catalyzes the ATP-dependent conversion of ribose-5-phosphate to phosphoribosyl pyrophosphate. The reaction product is a key precursor for the biosynthesis of purine and pyrimidine nucleotides. RESULTS: We report the 2.2 Å crystal structure of the E. coli ribose-phosphate pyrophosphobinase (EcKPRS). The protein has two type I phosphoribosyltransferase folds, related by 2-fold pseudosymmetry. The propeller-shaped homohexameric structure of KPRS is composed of a trimer of dimers, with the C-terminal domains forming the dimeric blades of the propeller and the N-terminal domains forming the hexameric core. The key, conserved active site residues are well-defined in the structure and positioned appropriately to bind substrates, adenosine monophosphate and ribose-5-phosphate. The allosteric site is also relatively well conserved but, in the EcKPRS structure, several residues from a flexible loop occupy the site where the allosteric modulator, adenosine diphosphate, is predicted to bind. The presence of the loop in the allosteric site may be an additional level of regulation, whereby low affinity molecules are precluded from binding. CONCLUSIONS: Overall, this study details key structural features of an enzyme that catalyzes a critical step in nucleotide metabolism. This work provides a framework for future studies of this important protein and, as nucleotides are critical for viability, may serve as a foundation for the development of novel anti-bacterial drugs.
Source: BMC Structural Biology
Institutions: Stony Brook University, SUNY Cortland
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,170
Funders: National Science Foundation, U.S. Department of Energy, National Institutes of Health, Directorate for Biological Sciences, Office of Science, National Institute of General Medical Sciences, National Center for Research Resources, Office of Research Infrastructure Programs, National Institutes of Health, Argonne National Laboratory
Awards: G102163711, G107546177, G1313983767, Mechanisms that govern assembly and function of higher order protein structures of purine metabolic enzymes, G1505794299, G1664757510, G2101401529, G2164036156, G2287611682, G254657075, G262962599, G2686365521, G2887060908, G3075337988, Pixel Array Detector for X-ray Crystallography, G340565428, G3407338877, G409777406, G498139845, G5106849484, G513797252, G5201631574, G5607048534, G5915780612, CAREER: Structural dynamics and mechanisms of photoreceptor signaling, G666778509, IDBR: TYPE A Precise Manipulation and Patterning of Protein Nanocrystals Using Surface Acoustic Wave Technology, G6848031779, G6918803902, G7368700025, G737631362, G7946479114, NE-CAT Center for Advanced Macromolecular Crystallography, G9000119994, G921583954, G969889393, G993149817
OpenAlex ID: W2912453854