Hyaluronan Synthase: The Mechanism of Initiation at the Reducing End and a Pendulum Model for Polysaccharide Translocation to the Cell Exterior

Figure 2

Membrane organization of HAS domains and conserved potential glycosyl-UDP binding regions. The experimentally determined topology of SpHAS [28] is modified to incorporate the discovery [46] that all four Cys residues of SeHAS (white circles) are at the membrane-protein interface and are located in or very near to the sugar-UDP binding sites. These four Cys residues are positionally conserved in the Class I HAS family. The SeHAS numbering shows the amino acids at the cytoplasmic junctions of the six MDs (white numbers 1–6). The parallel lines (gray) between C262 and C281 indicate the close proximity (~5 A) of these residues; they are not disulfide bonded. Eight “DXD”- or “XDD”-equivalent motifs in SeHAS, potential glycosyl-UDP binding sites (rectangle boxes), are either conserved just among the streptococcal enzymes (light gray) or also among the eukaryotic HASs (white); a few exceptions are discussed in the text. In some motifs, a streptococcal acidic residue is shaded white to indicate its conservation in the HAS family.