| Structural highlights
Function
KPRS_ECOLI Involved in the biosynthesis of the central metabolite phospho-alpha-D-ribosyl-1-pyrophosphate (PRPP) via the transfer of pyrophosphoryl group from ATP to 1-hydroxyl of ribose-5-phosphate (Rib-5-P).[HAMAP-Rule:MF_00583][1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
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 A 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.
Crystal structure of E. coli PRPP synthetase.,Zhou W, Tsai A, Dattmore DA, Stives DP, Chitrakar I, D'alessandro AM, Patil S, Hicks KA, French JB BMC Struct Biol. 2019 Jan 15;19(1):1. doi: 10.1186/s12900-019-0100-4. PMID:30646888[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Bower SG, Harlow KW, Switzer RL, Hove-Jensen B. Characterization of the Escherichia coli prsA1-encoded mutant phosphoribosylpyrophosphate synthetase identifies a divalent cation-nucleotide binding site. J Biol Chem. 1989 Jun 15;264(17):10287-91. PMID:2542328
- ↑ Hove-Jensen B, Harlow KW, King CJ, Switzer RL. Phosphoribosylpyrophosphate synthetase of Escherichia coli. Properties of the purified enzyme and primary structure of the prs gene. J Biol Chem. 1986 May 25;261(15):6765-71. PMID:3009477
- ↑ Hove-Jensen B, Nygaard P. Phosphoribosylpyrophosphate synthetase of Escherichia coli, Identification of a mutant enzyme. Eur J Biochem. 1982 Aug;126(2):327-32. doi: 10.1111/j.1432-1033.1982.tb06782.x. PMID:6290219 doi:https://dx.doi.org/10.1111/j.1432-1033.1982.tb06782.x
- ↑ Hilden I, Hove-Jensen B, Harlow KW. Inactivation of Escherichia coli phosphoribosylpyrophosphate synthetase by the 2',3'-dialdehyde derivative of ATP. Identification of active site lysines. J Biol Chem. 1995 Sep 1;270(35):20730-6. doi: 10.1074/jbc.270.35.20730. PMID:7657655 doi:https://dx.doi.org/10.1074/jbc.270.35.20730
- ↑ Willemoes M, Nilsson D, Hove-Jensen B. Effects of mutagenesis of aspartic acid residues in the putative phosphoribosyl diphosphate binding site of Escherichia coli phosphoribosyl diphosphate synthetase on metal ion specificity and ribose 5-phosphate binding. Biochemistry. 1996 Jun 25;35(25):8181-6. doi: 10.1021/bi9528560. PMID:8679571 doi:https://dx.doi.org/10.1021/bi9528560
- ↑ Willemoes M, Hove-Jensen B. Binding of divalent magnesium by Escherichia coli phosphoribosyl diphosphate synthetase. Biochemistry. 1997 Apr 22;36(16):5078-83. doi: 10.1021/bi962610a. PMID:9125530 doi:https://dx.doi.org/10.1021/bi962610a
- ↑ Zhou W, Tsai A, Dattmore DA, Stives DP, Chitrakar I, D'alessandro AM, Patil S, Hicks KA, French JB. Crystal structure of E. coli PRPP synthetase. BMC Struct Biol. 2019 Jan 15;19(1):1. doi: 10.1186/s12900-019-0100-4. PMID:30646888 doi:https://dx.doi.org/10.1186/s12900-019-0100-4
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