Similar active sites in lysostaphins and D-Ala-D-Ala metallopeptidases.
Specific peptidases exist for nearly every amide linkage in peptidoglycan. In several cases, families of peptidoglycan hydrolases with different specificities turned out to be related. Here we show that lysostaphin-type peptidases and D-Ala-D-Ala metallopeptidases have similar active sites and share a core folding motif in otherwise highly divergent folds. The central Zn(2+) is tetrahedrally coordinated by two histidines, an aspartate, and a water molecule. The Zn(2+) chelating residues occur in the order histidine, aspartate, histidine in all sequences and contact the metal via the Nepsilon, the Odelta, and the Ndelta, respectively. The identity of the other active-site residues varies, but in all enzymes of known structure except for VanX, a conserved histidine is present two residues upstream of the second histidine ligand to the Zn(2+). As the same arrangement of active-site residues is also found in the N-terminal, cryptic peptidase domain of sonic hedgehog, we propose that this arrangement of active-site residues be called the "LAS" arrangement, because it is present in lysostaphin-type enzymes, D-Ala-D-Ala metallopeptidases, and in the cryptic peptidase in the N-domain of sonic hedgehog.
Bochtler
Matthias
M
IIMCB, Trojdena 4, 02-109 Warsaw, Poland. MBochtler@iimcb.gov.pl
Odintsov
Sergey G
SG
Marcyjaniak
Malgorzata
M
Sabala
Izabela
I
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D053823:Hedgehog Proteins; D008024:Ligands; D045726:Metalloproteases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013302:Streptomyces / Q000737:chemistry / Q000201:enzymology*; D040681:Structural Homology, Protein; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
D001426:Bacterial Proteins; D053823:Hedgehog Proteins; D008024:Ligands; D015534:Trans-Activators; D010450:Endopeptidases; D045726:Metalloproteases; C120985:LytM protein, Staphylococcus aureus; D015032:Zinc