Human Peptidoglycan Recognition Protein-L Is an N-Acetylmuramoyl-L-alanine Amidase

Peptidoglycan recognition proteins (PGRPs)

“…Digestion of peptidoglycan with amidase reduces or eliminates the ability of polymeric peptidoglycan to stimulate insect cells [14], and thus the function of amidase PGRPs in vivo may be to prevent excessive activation of the immune system by bacteria [39,40]. On the basis of the conserved structure of the active site of the amidase, several other insect PGRPs are predicted to have amidase activity, whereas several others are not [9,14,15] (Figure 1 and Table 1). One PGRP that is not an amidase, Drosophila PGRP-SA, has an L,D-carboxypeptidase activity with specificity for the bond between DAP and D-Ala of the stem peptide present in peptidoglycan of Gramnegative bacteria and Gram-positive rod bacteria [12] ( Figure 4).…”

“…Crystallographic analysis of human PGLYRP-1 and the carboxy-terminal PGRP domain of PGLYRP-3, as well as insect PGRP-LB, -SA, -LC and -LE, show that all these PGRPs have a ligand-binding groove that binds peptidoglycan and is specific for MurNAc bound to three peptide-bonded amino acids (muramyl-tripeptide), which is the minimum peptidoglycan fragment hydrolyzed by PGLYRP-2 [7,9,[10][11][12][13][52][53][54][55]. It can accommodate a larger structure, such as GlcNAcMurNAc-tetrapeptide or MurNAc-pentapeptide (Figure 3), but it does not bind muramyl-dipeptide or a peptide without MurNAc [56][57][58].…”

“…‡ A dash in the PBD ID column indicates that a structure or function has not been determined. § Amidase activities were predicted on the basis of the presence of all four Zn 2+ -binding amino acids and other amino acids required for the amidase activity, as described [9,14,15]. PPO, prophenol-oxidase.…”

Molecular and functional characterization of peptidoglycan-recognition protein SC2 (PGRP-SC2) from Nile tilapia (Oreochromis niloticus) involved in the immune response to Streptococcus agalactiae

“…Almost all PGRPs have two closely spaced conserved cysteines in the PGRP domain that form a disulfide bond, which is needed for the activity of PGRPs [7,8]. All amidase-active PGRPs have a conserved Zn 2þ -binding site in the peptidoglycan-binding groove, which consists of two histidines, one tyrosine, and one cysteine [9e11].…”

Molecular cloning and functional characterization of peptidoglycan recognition protein 6 in grass carp Ctenopharyngodon idella

“…PGLYRP1 is found mainly in granules of polymorphonuclear leukocytes; PGLYRP2 is expressed mainly in liver, and PGLYRP3 and PGLYRP4 are selectively expressed in skin, eyes, salivary glands, tongue, throat, esophagus, stomach and intestine (Kashyap et al, 2011). Initially, mammalian PGRPs were reported to have two major functions: amidase activity and antibacterial activity (Wang et al, 2003;Dziarski and Gupta, 2006). Recently, it has been suggested that mammalian PGRPs have a role in modulating inflammation and immune responses (Saha et al, 2009(Saha et al, , 2010Park et al, 2011;Zenhom et al, 2011).…”