Selective recognition of synthetic lysine and meso-diaminopimelic acid-type peptidoglycan fragments by human peptidoglycan recognition proteins Iα and S

The interactions of a range of synthetic peptidoglycan derivatives with PGRP-I alpha and PGRP-S have been studied in real-time using surface plasmon resonance. A dissociation constant of K-D = 62 mu M was obtained for the interaction of peptidoglycan recognition protein (PGRP)-I alpha with the lysine-containing muramyl pentapeptide ( compound 6). The normalized data for the lysine-containing muramyl tetra- ( compound 5) and pentapeptide ( compound 6) showed that these compounds have similar affinities, whereas a much lower affinity for muramyl tripeptide ( compound 3) was measured. Similar affinities were obtained when the lysine moiety of the muramyl peptides was replaced by meso-diaminopimelic acid (DAP). Furthermore, the compounds that contained only a stem peptide ( pentapeptide, compound 1) and (DAP-PP, compound 2) as well as muramyldipeptide ( compound 3) exhibited no binding indicating that the muramyltripeptide ( compound 4) is the smallest peptidoglycan fragment that can be recognized by PGRP-I alpha. Surprisingly, PGRP-S derived significantly higher affinities for the DAP-containing fragments to similar lysine-containing derivatives, and the following dissociation constants were measured: muramylpentapeptide-DAP, K-D = 104 nM; muramyltetrapeptide-DAP, 92.4 nM; and muramyltripeptide-DAP, 326 nM. The binding profiles were rationalized by using a recently reported x-ray crystal structure of PGRP-I alpha with the lysine-containing muramyltripeptide (4).