Conformation and dynamics of heparin and heparan sulfate

The glycosaminoglycans heparin and heparan sulfate contain similar structur al units in varying proportions providing considerable diversity in sequenc e and biological function. Both compounds are alternating copolymers of glu cosamine with both iduronate- and glucuronate-containing sequences bearing N-sulfate, N-acetyl, and O-sulfate substitution. Protein recognition of the se structurally-diverse compounds depends upon substitution pattern, overal l molecular shape, and on internal mobility. In this review particular atte ntion is paid to the dynamic aspects of heparin/heparan sulfate conformatio n. The iduronate residue possesses an unusually flexible pyranose ring conf ormation. This extra source of internal mobility creates special problems i n rationalization of experimental data for these compounds. We present here in the solution-state NMR parameters, fiber diffraction data, crystallograp hic data, and molecular modeling methods employed in the investigation of h eparin and heparan sulfate. Heparin is a useful model compound for the sulf ated, protein-binding regions of heparan sulfate. The literature contains a number of solution and solid-state studies of heparin oligo- and polysacch arides for both isolated heparin species and those bound to protein recepto rs, These studies indicate a diversity of iduronate ring conformations, but a limited range of glycosidic linkage geometries in the repeating disaccha rides. In this sense, heparin exhibits a well-defined overall shape within which iduronate ring forms can freely interconvert. Recent work suggests th at computational modeling could potentially identify heparin binding sites on protein surfaces.