A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Reassessing the substrate specificities of the major Staphylococcus aureus peptidoglycan hydrolases lysostaphin and LytM (2024)

Antenucci, L., Virtanen, S., Thapa, C., Jartti, M., Pitkänen, I., Tossavainen, H., & Permi, P. (2024). Reassessing the substrate specificities of the major Staphylococcus aureus peptidoglycan hydrolases lysostaphin and LytM. eLife, 13, Article RP93673. https://doi.org/10.7554/eLife.93673

JYU-tekijät tai -toimittajat

Antenucci, Lina
Thapa, Chandan
Jartti, Minne
Pitkänen, Ilona
Aitio, Helena
Permi, Perttu

Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: Antenucci, Lina; Virtanen, Salla; Thapa, Chandan; Jartti, Minne; Pitkänen, Ilona; Tossavainen, Helena; Permi, Perttu

Lehti tai sarja: eLife

eISSN: 2050-084X

Julkaisuvuosi: 2024

Ilmestymispäivä: 04.11.2024

Volyymi: 13

Artikkelinumero: RP93673

Kustantaja: eLife Sciences Publications

Julkaisumaa: Britannia

Julkaisun kieli: englanti

DOI: https://doi.org/10.7554/eLife.93673

Julkaisun avoin saatavuus: Avoimesti saatavilla

Julkaisukanavan avoin saatavuus: Kokonaan avoin julkaisukanava

Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/98278

Rinnakkaistallenteen verkko-osoite (pre-print): https://doi.org/10.1101/2023.10.13.562287

Tiivistelmä

Orchestrated action of peptidoglycan (PG) synthetases and hydrolases is vital for bacterial growth and viability. Although the function of several PG synthetases and hydrolases is well understood, the function, regulation, and mechanism of action of PG hydrolases characterised as lysostaphin-like endopeptidases have remained elusive. Many of these M23 family members can hydrolyse glycyl-glycine peptide bonds and show lytic activity against Staphylococcus aureus whose PG contains a pentaglycine bridge, but their exact substrate specificity and hydrolysed bonds are still vaguely determined. In this work, we have employed NMR spectroscopy to study both the substrate specificity and the bond cleavage of the bactericide lysostaphin and the S. aureus PG hydrolase LytM. Yet, we provide substrate-level evidence for the functional role of these enzymes. Indeed, our results show that the substrate specificities of these structurally highly homologous enzymes are similar, but unlike observed earlier both LytM and lysostaphin prefer the D-Ala-Gly cross-linked part of mature peptidoglycan. However, we show that while lysostaphin is genuinely a glycyl-glycine hydrolase, LytM can also act as a D-alanyl-glycine endopeptidase.

YSO-asiasanat: infektiotaudit; NMR-spektroskopia; stafylokokit; mikrobiologia; bakteriologia; biokemia

Vapaat asiasanat: LytM; NMR spectroscopy; S. aureus; biochemistry; chemical biology; infectious disease; lysostaphin; microbiology; peptidoglycan hydrolases; substrate specificity.

Liittyvät organisaatiot

Hankkeet, joissa julkaisu on tehty

OKM-raportointi: Kyllä

VIRTA-lähetysvuosi: 2024

Alustava JUFO-taso: 2