AmpD, essential for both beta-lactamase regulation and cell wall recycling, is a novel cytosolic N-acetylmuramyl-L-alanine amidase.
In enterobacteria, the ampD gene encodes a cytosolic protein which acts as a negative regulator of beta-lactamase expression. It is shown here that the AmpD protein is a novel N-acetylmuramyl-L-alanine amidase (E.C.3.5.1.28) participating in the intracellular recycling of peptidoglycan fragments. Surprisingly, AmpD exhibits an exclusive specificity for substrates containing anhydro muramic acid. This anhydro bond is mainly found in the peptidoglycan degradation products formed by the periplasmic lytic transglycosylases and thus might behave as a 'recycling tag' allowing the enzyme to distinguish these fragments from the newly synthesized peptidoglycan precursors. The AmpD substrate (or substrates) which accumulates in the absence of the corresponding enzymatic activity acts as an intracellular positive effector for beta-lactamase expression and might represent an element of a communication network between the chromosome and the cell wall peptidoglycan.
Jacobs
C
C
Centre d'Ingénierie des Protéines, Université de Liège, Belgium.
Joris
B
B
Jamin
M
M
Klarsov
K
K
Van Beeumen
J
J
Mengin-Lecreulx
D
D
van Heijenoort
J
J
Park
J T
JT
Normark
S
S
Frère
J M
JM
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D002240:Carbohydrate Sequence; D002473:Cell Wall / Q000378:metabolism*; D016971:Citrobacter freundii / Q000201:enzymology / Q000235:genetics; D003001:Cloning, Molecular; D003600:Cytosol / Q000201:enzymology; D004790:Enzyme Induction; D015964:Gene Expression Regulation, Bacterial; D006020:Glycopeptides / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics / Q000502:physiology*; D010457:Peptidoglycan / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013379:Substrate Specificity; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics
C084284:AmpG protein, Bacteria; D001426:Bacterial Proteins; D006020:Glycopeptides; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D010457:Peptidoglycan; C062460:AmpD protein, Bacteria; D009238:N-Acetylmuramoyl-L-alanine Amidase; C048795:AmpC beta-lactamases; D001618:beta-Lactamases