Fig. 6: Model of HA synthesis and translocation.
From: Structural insights into translocation and tailored synthesis of hyaluronan
(1) A GlcNAc monosaccharide released from UDP-GlcNAc primes HAS. (2) Coordination of UDP-GlcA at the active site repositions the primer to accommodate the donor glycosyl unit. Transient interactions between the nucleotide and the gating loop likely stabilize the loop (dashed versus solid green line) and contribute to catalytic activity. (3) Glycosyl transfer and UDP release generate a disaccharide-bound state with GlcA extending into the catalytic pocket. (4) UDP-GlcNAc binding correlates with disaccharide translocation to position GlcA at the acceptor site. (5) Glycosyl transfer and UDP release produce a trisaccharide that translocates into the channel after rotation of the nonreducing end terminal GlcNAc unit. (6) After multiple cycles of substrate turnover, the nascent HA chain induces channel opening (see Supplementary Discussion for more information).
