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A distinctive family of L,D-transpeptidases catalyzing L-Ala-mDAP crosslinks in Alpha- and Betaproteobacteria

Espaillat, Akbar, master, 1988- (author)
Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten),Chr. Hansen A/S, Microbial Physiology, R & amp;D, Hoersholm, Denmark
Alvarez, Laura (author)
Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
Torrens, Gabriel (author)
Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
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ter Beek, Josy (author)
Umeå universitet,Institutionen för medicinsk kemi och biofysik,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)
Miguel-Ruano, Vega (author)
Department of Crystallography and Structural Biology, Institute of Physical Chemistry “Blas Cabrera”, CSIC, Madrid, Spain
Irazoki, Oihane (author)
Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
Gago, Federico (author)
Department of Biomedical Sciences & amp; IQM-CSIC Associate Unit, School of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain
Hermoso, Juan A. (author)
Department of Crystallography and Structural Biology, Institute of Physical Chemistry “Blas Cabrera”, CSIC, Madrid, Spain
Berntsson, Ronnie P-A. (author)
Umeå universitet,Institutionen för medicinsk kemi och biofysik,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)
Cava, Felipe (author)
Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
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 (creator_code:org_t)
Springer Nature, 2024
2024
English.
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • The bacterial cell-wall peptidoglycan is made of glycan strands crosslinked by short peptide stems. Crosslinks are catalyzed by DD-transpeptidases (4,3-crosslinks) and LD-transpeptidases (3,3-crosslinks). However, recent research on non-model species has revealed novel crosslink types, suggesting the existence of uncharacterized enzymes. Here, we identify an LD-transpeptidase, LDTGo, that generates 1,3-crosslinks in the acetic-acid bacterium Gluconobacter oxydans. LDTGo-like proteins are found in Alpha- and Betaproteobacteria lacking LD3,3-transpeptidases. In contrast with the strict specificity of typical LD- and DD-transpeptidases, LDTGo can use non-terminal amino acid moieties for crosslinking. A high-resolution crystal structure of LDTGo reveals unique features when compared to LD3,3-transpeptidases, including a proline-rich region that appears to limit substrate access, and a cavity accommodating both glycan chain and peptide stem from donor muropeptides. Finally, we show that DD-crosslink turnover is involved in supplying the necessary substrate for LD1,3-transpeptidation. This phenomenon underscores the interplay between distinct crosslinking mechanisms in maintaining cell wall integrity in G. oxydans.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

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