| Structural highlights
Function
PURNU_ECOLI Purine nucleoside enzyme that catalyzes the phosphorolysis of adenosine and inosine nucleosides, yielding D-ribose 1-phosphate and the respective free bases, adenine and hypoxanthine (PubMed:31978345). Also catalyzes the phosphorolysis of S-methyl-5'-thioadenosine into adenine and S-methyl-5-thio-alpha-D-ribose 1-phosphate (PubMed:31978345). Also has adenosine deaminase activity (PubMed:31978345). May also act as a polyphenol oxidase: able to oxidize syringaldazine and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) in vitro (PubMed:16740638).[1] [2]
Publication Abstract from PubMed
Bacterial cells are encased in peptidoglycan (PG), a polymer of disaccharide N-acetylglucosamine (GlcNAc) and N-acetyl-muramic acid (MurNAc) cross-linked by peptide stems. PG is synthesized in the cytoplasm as UDP-MurNAc-peptide precursors, of which the amino acid composition of the peptide is unique, with l-Ala added at the first position in most bacteria but with l-Ser or Gly in some bacteria. YfiH is a PG-editing factor whose absence causes misincorporation of l-Ser instead of l-Ala into peptide stems, but its mechanistic function is unknown. Here, we report the crystal structures of substrate-bound and product-bound YfiH, showing that YfiH is a cytoplasmic amidase that controls the incorporation of the correct amino acid to the nucleotide precursors by preferentially cleaving the nucleotide precursor by-product UDP-MurNAc-l-Ser. This work reveals an editing mechanism in the cytoplasmic steps of peptidoglycan biosynthesis. IMPORTANCE YfiH is a peptidoglycan (PG)-editing factor required for the maintenance of specific amino acid compositions of the stem peptides. However, the activity of YfiH has not been deciphered, and the editing mechanism involving YfiH has remained a mystery. Through X-ray crystallographic and biochemical analyses, we demonstrate that YfiH is a hydrolase with a previously unknown activity specific for the UDP-MurNAc-monopeptide, one of the nucleotide precursors from the cytoplasmic steps of the PG biosynthesis pathway. YfiH selectively hydrolyzes UDP-MurNAc-Ser, an incorrect by-product of the biosynthesis reaction, to ensure that only the correct PG precursor, UDP-MurNAc-Ala, is incorporated. Therefore, this work reveals coupled synthetic and editing reactions in the cytoplasmic steps of PG biosynthesis.
Structural Basis for the Peptidoglycan-Editing Activity of YfiH.,Lee MS, Hsieh KY, Kuo CI, Lee SH, Garde S, Reddy M, Chang CI mBio. 2022 Feb 15:e0364621. doi: 10.1128/mbio.03646-21. PMID:35164571[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Beloqui A, Pita M, Polaina J, Martinez-Arias A, Golyshina OV, Zumarraga M, Yakimov MM, Garcia-Arellano H, Alcalde M, Fernandez VM, Elborough K, Andreu JM, Ballesteros A, Plou FJ, Timmis KN, Ferrer M, Golyshin PN. Novel polyphenol oxidase mined from a metagenome expression library of bovine rumen: biochemical properties, structural analysis, and phylogenetic relationships. J Biol Chem. 2006 Aug 11;281(32):22933-42. doi: 10.1074/jbc.M600577200. Epub 2006, Jun 1. PMID:16740638 doi:http://dx.doi.org/10.1074/jbc.M600577200
- ↑ Cader MZ, de Almeida Rodrigues RP, West JA, Sewell GW, Md-Ibrahim MN, Reikine S, Sirago G, Unger LW, Iglesias-Romero AB, Ramshorn K, Haag LM, Saveljeva S, Ebel JF, Rosenstiel P, Kaneider NC, Lee JC, Lawley TD, Bradley A, Dougan G, Modis Y, Griffin JL, Kaser A. FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle. Cell. 2020 Jan 23;180(2):278-295.e23. doi: 10.1016/j.cell.2019.12.017. PMID:31978345 doi:http://dx.doi.org/10.1016/j.cell.2019.12.017
- ↑ Lee MS, Hsieh KY, Kuo CI, Lee SH, Garde S, Reddy M, Chang CI. Structural Basis for the Peptidoglycan-Editing Activity of YfiH. mBio. 2022 Feb 15:e0364621. doi: 10.1128/mbio.03646-21. PMID:35164571 doi:http://dx.doi.org/10.1128/mbio.03646-21
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