Latent LytM at 1.3A resolution.
LytM, an autolysin from Staphylococcus aureus, is a Zn(2+)-dependent glycyl-glycine endopeptidase with a characteristic HxH motif that belongs to the lysostaphin-type (MEROPS M23/37) of metallopeptidases. Here, we present the 1.3A crystal structure of LytM, the first structure of a lysostaphin-type peptidase. In the LytM structure, the Zn(2+) is tetrahedrally coordinated by the side-chains of N117, H210, D214 and H293, the second histidine of the HxH motif. Although close to the active-site, H291, the first histidine of the HxH motif, is not directly involved in Zn(2+)-coordination, and there is no water molecule in the coordination sphere of the Zn(2+), suggesting that the crystal structure shows a latent form of the enzyme. Although LytM has not previously been considered as a proenzyme, we show that a truncated version of LytM that lacks the N-terminal part with the poorly conserved Zn(2+) ligand N117 has much higher specific activity than full-length enzyme. This observation is consistent with the known removal of profragments in other lysostaphin-type proteins and with a prior observation of an active LytM degradation fragment in S.aureus supernatant. The "asparagine switch" in LytM is analogous to the "cysteine switch" in pro-matrix metalloproteases.
Odintsov
Sergey G
SG
International Institute of Molecular and Cell Biology, ul. Trojdena 4, 02-109 Warsaw, Poland.
Sabala
Izabela
I
Marcyjaniak
Malgorzata
M
Bochtler
Matthias
M
D001426:Bacterial Proteins / Q000737:chemistry* / Q000302:isolation & purification; D001665:Binding Sites; D018360:Crystallography, X-Ray; D010450:Endopeptidases / Q000737:chemistry* / Q000302:isolation & purification; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000737:chemistry; D008248:Lysostaphin / Q000737:chemistry; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D015032:Zinc / Q000737:chemistry
D001426:Bacterial Proteins; D004792:Enzyme Precursors; D010450:Endopeptidases; D008248:Lysostaphin; C120985:LytM protein, Staphylococcus aureus; D015032:Zinc